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Notes on Tumors 



FRANCIS CARTER WOOD 



NEW YORK 

1920 






COPYRIGHT, 1920 

BY 

J. T. DOUGHERTY 

NEW YORK 



m 2A fS20 
©GIA570126 



PREFACE 

These notes have been prepared solely for the use of 
students in tumor pathology and of hospital internes, and 
there have been omitted, therefore, some of the more gen^ 
eral questions concerning neoplasms; these will be found 
discussed in the reference works, a list of which is ap- 
pended. In order to increase the usefulness of the book 
certain ^ypes of tumors have been described which, on 
account of their rarity, will not be ordinarily studied, the 
limited time given for instruction being better applied to 
the study of the more frequently occurring varieties which 
are seen daily in the hospitals. 

A fair amount of bibliography has been included, not 
with the idea that the student will have sufficient time to 
read the original papers during the course, but in order 
that, if he is interested in further study of the subject and 
wishes to obtain the valuable training which a careful 
perusal of the original sources affords to any but the most 
superficial, he will find enough to enable him to look up 
the most important monographs on the subject. 



BIBLIOGRAPHY OF TUMORS 

A most important book on tumors and one that may 
still be consulted with profit by the student of oncology is 
Rudolf Virchow's Die Krankhaften Geschwiilste, Berlin, 
1863. This work was, unfortunately, never completed by 
its famous author, but it contains many valuable observa- 
tions on tumors. The general literature of the subject and 
a thorough resume of various methods of treatment, etc., 
are contained in Wolff: Die Lehre von der Krebskrankheit, 
Jena, 1914. Borst: Die Lehre von den Geschwiilsten, Wies- 
baden, 1902, is an exceedingly valuable work with beautiful 
illustrations and a very complete bibliography. Ribbert: 
Geschwiilstlehre, 2d ed., Bonn, 1914, and Das Karzinom des 
Menschen, Bonn, 1911, contain complete surveys of the 
morphological side of the tumor question, influenced largely 
by the writer's very strong personal views, but nevertheless 
absolutely invaluable to the student of pathology. Ewing: 
Neoplastic Diseases, Philadelphia, 1919, is the most recent 
contribution to the subject; it contains a vast store of 
information and a considerable bibliography. For the occur- 
rence of tumors in early childhood, see Merkel: Briining 
and Schwalbe's Handbuch der allgemeinen Pathologie und 
der pathologischen Anatomie des Kindesalters, Wiesbaden, 

4 



1912. Williams: Natural History of Cancer, New York, 
1908, is a useful, semi-popular survey of the subject. Bland- 
Sutton: Tumors Innocent and Malignant, New York, 1917, 
is now in many ways out of date, but contains many inter- 
esting descriptions and illustrations of rare tumors, a num- 
ber of them in animals. Cullen : Cancer of the Uterus, New 
York, 1900 ; and Kelly and Cullen : Myomata of the Uterus, 
Philadelphia, 1909, are beautifully illustrated monographs 
on special forms of growths as indicated by the titles. 
From the purely diagnostic side, v. Hansemann : Die mikros- 
kopische Diagnose der bosartigen Geschwiilste, Berlin, 1902, 
is excellent. An inexhaustible source book of gynecological 
pathology is Veit : Handbuch der Gynakologie, 2d ed., Wies- 
baden, 1908. Much has been learned of cancer by the 
experimental method, and the best review of the subject 
is in Woglom: The Study of Experimental Cancer, New 
York, 1912. The most important monographic collections 
on experimental cancer are the Scientific Reports of the 
Imperial Cancer Research Fund, London, 1908-1920. The 
volumes of Lubarsch-Ostertag's Ergebnisse der allgemeinen 
Pathologie contain many excellent reviews of the current 
literature on cancer. 



GENERAL BIOLOGY OF TUMORS 

The word "tumor" was originally applied to any new 
growth. Since the introduction of the microscope, however, 
many of the inflammatory swellings have been excluded 
from the class of true tumors and the term is now limited 
to independent growths of tissue of which the cause is not 
known. This excludes tuberciilosis, syphilis, and other 
forms of tissue hyperplasia due to bacterial action inciting 
productive inflammation and also the regenerative hyper- 
plasias, such as an exuberant callus. 

Definition: A tumor is a more or less circumscribed 
collection of cells arising wholly independently of the rest 
of the body, in general growing progressively, and serving 
no useful purpose in the organism. It will be noticed that 
this is entirely a descriptive definition, for as we do not 
know the cause or causes of tumors it is impossible to 
define these structures more accurately. Some immediate 
exceptions to the definition will be noted. The first is that 
a tumor does not always grow progressively, but may 
remain stationary for a considerable period of time, or even 
retrogress. Also, a tumor may be of use to the body in 
supplying certain secretions, such as the specific thyroid 
material from a carcinoma of the thyroid ; but at the same 
time that it furnishes this secretion it grows into the tissues 
of the host and ultimately destroys the life of the organism 
which carries it. 

Structure: The cellular composition of tumors varies 
greatly in the different types. Common to almost all 
tumors is a connective tissue of the normal fibrous type, 

6 



carrying blood-vessels. Without some such blood supply a 
tumor cannot exist. The remaining structures of a 
neoplasm may comprise almost any of the tissues of the 
body. The most frequent, next to the connective tissue, 
are epithelial cells of varying types. Next in order of fre- 
quency are unstriated muscle tissue, cartilage, and bone. 
Striated muscle and nerve cells are rare components. In 
general, the cells of a tumor imitate to a certain extent 
the tissues from which the growth springs ; that is, a tumor 
of the breast is apt to contain structures reminiscent of 
the secreting glands of the mamma ; a tumor of the adrenal 
is apt to contain chromaffin cells; a tumor of the uterus, 
unstriated muscle; a carcinoma of the gut, glandular struc- 
tures which resemble more or less the normal structures 
of the intestine and secrete mucus. In a few instances the 
cells, as, for example, in the rhabdomyomata, are sugges- 
tive of the muscle fibers of the fetus, and in certain of the 
complex tumors portions of organs may develop, imperfect 
it is true, but still showing some of the structures of the 
adult organ. 

CLASSIFICATION OF TUMORS 

Inasmuch as we do not know the cause of tumors, it is 
impossible to make a strictly scientific classification of 
them. It is, therefore, most convenient to use a purely mor- 
phological basis for classification, drawn from the micro- 
scopic appearance of the tumors and the tissues from which 
they originate. Cysts are included with tumors because of 
their genetic relationship to new growths rather than to 
any other pathological condition. 

The three main groups will, therefore, consist of 
tumors formed of the connective tissues ; tumors of epithe- 
lium, and tumors composed of mixtures of tissues of various 



sorts. Such a classification takes no heed of the biological 
qualities of the different tumors which it includes, but by 
comparing the experience of the pathologist and the surgeon 
it is possible to correlate with a certain success the clinical 
course of a tumor with its morphology ; yet, even with all 
the accumulated experience, there are occasional tumors 
whose exact biological course cannot be prognosticated. 
Thus, a tumor morphologically resembling a fibroma may 
recur after complete removal. Inasmuch as fibromata do 
not, as a rule, recur it would be natural to consider that, 
since all portions of a tumor cannot be examined micro- 
scopically, somewhere in the growth was a small area of 
sarcoma which escaped observation, and that the recurrence 
took place from a minute particle left during operation 
of the malignant portion of the growth. Whether a fibroma 
can change into a sarcoma is a question which has been 
very much discussed and is doubtful. It is certain that the 
transplantation of tumors of animals resembling fibromata 
has been possible^ and in some instances fibromata have 
been transplanted for many generations, for example, 
Crocker Fund rat tumor No. 39, but if the later transplants 
of these very slow growing, non-metastasizing tumors are 
examined microscopically they will show a certain amount 
of tissue resembling a sarcoma. Hence, the probability is 
that the tumor was a sarcoma before it was transplanted 
and has not altered in type. 

Beginning epitheliomata, polypoid adenomata of the 
stomach and intestine, and cystadenomata of the breast 
are other examples of growths in which the microscope does 
not always permit a final opinion as to the future biological 
activity of the neoplasms. 

*Ribbert: Transplantation eines Fibroma beim Hunde. Centralbl. 
f. allg. Path., 1910, xxi. 625. 



Connective Tissue Tumors. 

Connective tissue tumors can be divided into those in 
which the substance of the growth is made up of adult, 
well developed, mature cells, and those in which the cells 
are less differentiated and do not resemble the cells of the 
adult as much as they do those of the embryo. In the first 
group belong the frequently occurring fibromata, lipomata, 
angiomata, osteomata, and chondromata, together with a 
few rarer tumors. In the second group are the sarcomata, 
composed of more or less immature or undifferentiated cells. 

While the individual cells of the tumors composed of 
adult tissue often resemble very closely the structures from 
which they spring, yet this resemblance is not carried out 
through the whole tumor. The tissue as a whole does not 
resemble perfectly normal tissue. For example, while the 
connective tissue cells of a fibroma are as individuals abso- 
lutely the same as those in the region from which this 
tumor has arisen, the general structure is different. It is 
apt to be either more or less cellular than the corresponding 
connective tissue. Blood-vessels also are thin-walled and in 
the denser types are practically absent over considerable 
areas. Lymph-channels are defective and the nerve fila- 
ments which may be present have no relationship with the 
tumor, merely passing through the growth to the normal 
structures which they supply. In the chondromata, also, 
the cartilage cells are not so regular in their structure as 
those in normal cartilage. In the osteomata, the bone cells 
and lamellae are not arranged as systematically as they are 
in normal bone. In angiomata, the blood-vessels are much 
thinner walled and the surrounding tissue is entirely dif- 
ferent from that of the normal structure. 

In the second group of connective tissue tumors, where 
the cells are immature, there are many subdivisions based 
almost entirely on morphological characteristics. The most 

9 



frequent type of sarcoma is one which is derived from 
fibrous connective tissue, the structure of which may vary 
from that of a tumor almost exactly resembling a fibroma 
up to that of a rapid growth which has not the slightest 
resemblance to any of the normal structures of the body, 
the cells being composed largely of slightly granular cyto- 
plasm without the characteristic fibrils of connective tissue ; 
the nuclei are on the average larger than normal and con- 
tain a greater amount of chromatin material. In the type 
which resembles normal fibrous tissue, collagenous material 
is produced. In those composed wholly of cells, almost no 
collagen is seen except along the thin-walled capillaries of 
the connective tissue trabeculse which divide portions of 
the tumor from each other. The vascular channels are 
much thinner than in any normal tissue, being composed 
often only of a single layer of endothelial cells, hence the 
tendency of the tumor cells to enter the circulation early 
and cause metastases. Other forms of the sarcomata, espe- 
cially those arising in the bone or periosteum, produce spe- 
cial interstitial tissue, either cartilaginous or bony, or an 
imperfect mixture of the two. This capacity to elaborate 
a special tissue is seen, also, in the metastases of sarcomata 
of this type, the osteoblastic or chondroblastic sarcomata. 

Epithelial Tumors. 

The epithelial tumors which contain cells of adult 
quality a£d which imitate more or less perfectly the struc- 
tures from which they originate are the papillomata and 
the adenomata. The papilloma, springing from the skin 
or mucous membrane, is a tumor in which there is thicken- 
ing of the epithelial layers, distortion of its relationship 
with the connective tissue which supports it, and sometimes 
a very considerable increase in this connective tissue, so as 
to render the diagnosis of papilloma questionable, in which 

10 



case the tumor may be described as a fibroma with epithelial 
covering. All transitions between these two forms are pos- 
sible. In the adenomata which spring from the glands of 
various portions of the body, the intestine, the breast, the 
salivary glands, and the prostate, the structures resemble 
more or less perfectly the original elements from which 
they are derived. The individual cells are apt to be much 
more nearly normal and resemble the adult cell much more 
closely than the general glandular reproduction, which is 
apt to be very imperfect. In the simple adenomata the 
epithelial cells are arranged in an orderly fashion on a base- 
ment membrane of connective tissue which limits the 
growth of the cells in that direction, and according to the 
gland structure from which they are derived, they are 
arranged either in a single layer as in the rectum, or in 
several layers, as in the breast. As the tumor proliferates, 
however, and alters its type, the epithelium may creep up 
into the lumen of the glands and even form solid masses 
such as are frequently seen in the cystadenomata of the 
breast. 

The carcinomata form a continuous morphological 
bridge between the adenomata, with normal gland-like 
structures, and rapidly growing malignant tumors almost 
wholly composed of epithelial cells which have lost almost 
all resemblance to the normal cells from which they sprang. 
Nevertheless, there are carcinomata which so closely re- 
semble normal structures as to compel their classification 
as malignant to be based largely upon their growth or 
metastatic capacities. 

Teratomata 

The tumors included under this heading are generally 
assumed to be due to developmental defects, displacements, 
or over-production of tissue. The simplest type are the 

11 



epidermoid cysts which form about the eye, at the root of 
the nose, or on other parts of the face, where portions of 
the epidermis are left in the course of embryonic develop- 
ment of the skin. These cysts are composed of epidermis 
surrounding a mass of desquamated and fatty epithelial 
cells. A slightly more complex type contains hair and 
sebaceous follicles, due to a segregation of the skin at a 
little later stage of development. In this same class, also 
hardly to be considered as teratomata, are the congenital 
angiomata and the pigmented moles. Another form of 
somewhat more complex tumors derived from congenital 
defects are the branchiogenetic cysts which occur at the 
lateral aspect of the neck and are lined either with 
squamous epithelium or cylindrical or ciliated epithelium, 
depending upon whether they originate in the outer portion 
of the branchial cleft or the pharyngeal aspect. A different 
type of still greater complexity are the so-called "mixed," 
"complex," or "composite" tumors which appear chiefly in 
certain glands, including the parotid, submaxillary, sub- 
lingual and lacrimal (but not the pancreas), which contain 
mixtures of varying proportions of squamous epithelial or 
glandular remnants, myxomatous tissue, cartilage, bone, 
and even striated muscle. The next subdivision in com- 
plexity includes the mixed tumors of the kidney, vagina, 
bladder, prostate, vas deferens, ovary, and testicle. The 
theory is that these neoplasms have their origin in tissue 
displaceipents occurring during development, but at a fairly 
late period in fetal life; for example, the muscle tissue in 
the complex tumors of the kidney is referable to displace- 
ment of a portion of one of the myotomes. A third group 
comprises tumors of the ovary, testis, mediastinum, brain 
and sacral and retroperitoneal regions which contain rem- 
nants, either embryonic or adult, of tissues derived from 
all three germinal layers, and hence must be due to the 
segregation of unused blastomeres at an earlier stage in 

12 



fetal development than the preceding group of tumors. A 
fourth type, which contains even more completely developed 
tissue, are the tumors which are occasionally seen in the 
mediastinum and more frequently in the sacrum. They 
contain portions of fully developed organs and may even 
comprise a partially developed twin fetus. 

The simpler forms of teratoma are non-malignant. 
The very complex varieties are apt to form metastases of 
the connective tissue portions of the growth. For instance, 
the complex tumors of the kidney are almost always malig- 
nant, but the metastases are those of a sarcoma or carci- 
noma, and the muscle fibers and other elaborate structures 
almost never occur in the metastatic growths. 

The most frequent of all these complex tumors are the 
cystic embryomata of the ovary.^ These occur either in 
one or in both ovaries, and rarely exceed 10 cm. in diameter. 
They are filled with an oily fluid or a solid putty-like mass, 
composed of fat, desquamated epithelial cells, and more or 
less hair. The wall may be smooth and lined with epithe- 
lium, or a large portion of the epithelium may have desqua- 
mated. In one portion of the wall of the cyst there is 
usually a projection from which the hair grows. This 
rounded nodule corresponds roughly with the head of the 
undeveloped fetus, the cephalic end apparently retaining 
greater growth capacities than the extremities. In this 
mass can usually be demonstrated hair follicles and sebace- 
ous and sweat glands, and occasionally much more compli- 
cated structures. Remnants of pharyngeal or nasal mucous 
membrane with ciliated epithelium are often seen. Esopha- 
geal structures, sometimes gastric or intestinal mucous 
membrane, glia tissue with well marked rosettes, and occa- 
sionally brain tissue with ganglion cells, remnants of the 
choroid of the eye, thyroid tissue, and laryngeal cartilage 

^For full details see Askanazy: Die Dermoidcysten des Eierstocks, 
Bibliotheca Medica. Abt. C, Heft 19, Stuttgart, 1905 (bibl.) 

13 



may be found. The bone which is so often present is 
assumed to be that of the maxillae, and frequently contains 
well-formed teeth. The structures are all of adult type as 
compared to the embryonic tissues of the solid embryomata. 
In the epithelium covering the head nodule squamous-cell 
epithelioma may develop and give rise to metastases 
throughout the body, the tumor usually being highly malig- 
nant. The solid teratomata of the ovary on the other hand 
are rare. They are, as a rule, much larger than the dermoid 
cysts and are composed of a diffuse and complex mixture 
of various tissues of embryonic morphology, including carti- 
lage, bone, muscle, and all varieties of connective tissue, and 
are very frequently malignant, the dominating type of 
tumor cell being that of a sarcoma. 

A resume of the various classes of tumors is appended 
merely for the convenience of the student. As the arrange- 
ment is, as far as possible, histogenetic, it does not neces- 
sarily correspond with the clinical, regional, or biological 
classifications, and is in no sense final. 

Tumors of Supporting Tissue: 

Fibroma 

Myxoma 

Lipdma 

Xanthoma 

Chondroma 

Chordoma 

Osteoma 

Angioma 

Hemangioma 

Lymphangioma 

14 



Sarcoma 

Sarcoma from fibrous connective tissue 

Osteosarcoma 

Chondrosarcoma 

Myxosarcoma 

Giant-cell Sarcoma 

Angiosarcoma 

Alveolar Sarcoma 

Round-cell Sarcoma 

Lymphoblastoma 

Plasma-cell sarcoma 

Myeloma 

Chloroma 

Leukemia 

Tumors of Muscle Tissue 
Myoma 

Rhabdomyoma 

Leiomyoma 

Adenomyoma 

Malignant myoma (myosarcoma) 

Tumors of Pigment Cells 
Melanoma 

Melano-epithelioma 
Melanosarcoma 

Tumors of Endothelium 
Endothelioma 

Tumors of Nerve Structures 

Tumors derived from gliar tissue, glioma 
Tumors derived from nerve cells and nerve fibers 

15 



Tumors of Epithelium and Connective Tissue 

Papilloma 

Naevus 

Odontoma 

Cholesteatoma 

Adenoma 

Carcinoma 

Epithelioma 

Carcinoma 

Carcinoid tumors 
' Carcinosarcoma 
Chorionepithelioma 
Hypernephroma 

Teratoma 

L Displacements of single tissues 

1. Epidermoid cysts 

2. (a) Congenital moles 
(b) Angiomata 

II. Tumors arising in embryonic displacements of sev- 

eral tissues 

3. Complex salivary tumors. 

4. Complex solid tumors of kidney 

III. Tumors arising in embryonic remains of organs 

5. Branchiogenetic and other congenital cysts 

IV. Tumors arising in misplaced blastomeres or ova. 

6. Complex tumors of testicle 

7. Cystic or solid teratomata of ovary 

8. Cystic or solid teratomata containing adult 

tissues of a partially developed fetus 

Cysts 

16 



SPECIAL BIOLOGY OF TUMORS 

ETIOLOGY OF TUMORS 

The ultimate cause or causes of tumors are still un- 
known despite the clinical observations and theorizings of 
two thousand years. Greek and Roman physicians attri- 
buted cancer to some disturbance of the humoral balance 
of the body, the appearance of tumors being due to some 
alteration between the proportions of these hypothetical 
secretions. This idea recurs again and again in the history 
of cancer theories, and even today appears in the correla- 
tions which are hypothetically assumed to exist between 
alterations in the endocrine glands or their secretions and 
the appearance and growth of cancer.^ With the passing 
of humoral pathology and the discovery of the cell structure 
of the body, a crop of new theories sprang into being, of 
which only a few are of sufficient interest to warrant in- 
sertion here.2 

The first hypothesis greatly to influence the pathology 
of the time was that proposed by Virchow. He did much 
to clear up the relationship of the cells to tumors, asserted 
that neoplasms consist of normal tissue growing in a region 
in which it does not belong, and also called attention to the 
fact that the variation from the normal type of the tissue 
in which the tumor originated was the most important 
factor in the characterization of malignant new growths. 
While he early recognized the difference between sarcoma 
and carcinoma, he fell into the error of considering that 
the cells of the carcinoma sprang from connective tissue 
and were merely altered cells of that origin. 

^See Robertson and Ray: Jour. Biol. Chem., 1919 xxxvii, 427. 

^The student who wishes to learn more of the various hypotheses 
concerning- the cause and nature of cancer should consult Wolff: Die 
Lehre von der Krebskrankheit, Jena, 1907, volumes I and II, some 800 
pages of which are devoted to this question. Ribbert: Geschwulstlehre, 
2d ed., Bonn, 1914, and Karzinom des Menschen, Bonn, 1911, are valuable 
for reference. 

17 



Thiersch^ was the first to show that the carcinomata 
spring from epithelial cells, and applied in an expanded 
form Virchow's own dictum that all cells come from a cell 
of the same type. He saw, chiefly by studying small carci- 
nomata of the skin, that the epithelium is not derived from 
connective tissue, as supposed by Virchow, but springs from 
pre-existing epithelium. He recognized the fact that the 
connective tissue takes part in an inflammatory reaction 
about the epithelium, but plays only a subordinate part in 
the formation of a tumor. He held that a cancer originates 
when the static equilibrium which exists normally between 
the epithelium and connective tissue was in some way 
altered, permitting the penetration of the epithelium into 
the deeper layers; such penetration being favored by the 
softening of the stroma which occurs in old age. This, 
however, does not explain why the connective tissues form 
sarcomata nor why carcinomata occur in youthful persons. 

Waldeyer^ accepted Thiersch's ideas, expanded them 
by studies upon carcinomata of the breast, and explained 
the nature of metastatic growths which had puzzled 
Thiersch, showing that the tumor cells pass through the 
blood-vessels or lymphatics and when deposited in some 
distant region, for example, the lymph-nodes, give rise to 
fresh tumors, Waldeyer believed, in contrast to Thiersch, 
that the epithelial elements were separated by the growth 
of connective tissue, and when thus removed from their 
normal habitus, were capable of giving rise to a new growth, 
a view whicli Ribbert has recently expanded with modifica- 
tions into a theory of his own. 

Another hypothesis which has greatly influenced the 
study of the origin of m.alignant growths is that which 
bears the name of Cohnheim, although it was foreshadowed 
in the writings of others years before. This theory assumes 

^Thiersch: Der epithelial Krebs namentlich der Haut, Leipzig, 1865. 
2Waldeyer: Virchows Arch. f. path. Anat., 1867, xli, 479; 1872, Iv, 67. 

18 



that tumors are' based on the presence in the tissues of 
aberrant embryonic structures or cells which may remain 
quiescent for years, but ultimately under some stimulus 
develop into a new growth. Cohnheim's attention was 
called to this possibility of tissue displacement by the study 
of a mixed tumor of the kidney in which striated muscle 
was present, evidently a displacement of muscle cell tissue 
from the myotomes at an early stage of embryonic life. 
A large amount of discussion has centered about the Cohn- 
heim theory, perhaps more than about any other, and 
numerous writers have brought forth evidence to show that 
the postulated embryonal displacement of tissue is a not 
infrequent occurrence in the human body.^ Robert Meyer, 
who has made the most important contributions along this 
line, has shown that there are present in both sexes numer- 
ous heterotopic depositions of tissues of various types, that 
they are more numerous in old age than in youth, and that 
occasionally tumors arise in such aberrant masses. Rib- 
bert, also, in his numerous journal publications and his text 
books, has pointed out the necessity of assuming for certain 
types of tumors, especially the more complex ones, an 
embryonic displacement hypothesis such as Cohnheim 
brought forward. The difficulty of the whole question, and 
one of which Cohnheim himself was fully aware, is that 
mere displacement does not necessarily cause a tumor and 
that underlying the production of a neoplasm there is some- 
thing beyond the mere distortion of tissue relations. What 
that something was Cohnheim was unable to postulate. He 
thought that hyperemia might play some part. The most 
serious criticism of Cohnheim's theory has come from the 
observation that chronic irritation may give rise to a tumor 
in almost any portion of the body, and that, therefore, one 

iMeyer, R.: Lubarsch-Ostertag-, Ergebn. d. allg-. Path., 1905, ix', 
518; 1911, xvS 431. See also, Lubarsch: Verhandl. d. deutsch. Path. 
Gesells., 1906, x, 26; and Herxheimer: Gewebsmissbildungen, in Schwalbe: 
Handbuch der Missbildungen des Menschen, Jena, 1910, iii, 339. 

19 



must assume an extraordinary distribution of these hypo- 
thetical embryonic remnants, which differs in different 
races. For example, there is the well-known kangri cancer 
occurring in India where some of the hill tribes wear over 
the abdomen a small earthenware pot containing burning 
charcoal in order to keep their bodies warm, with the result 
that burns on the abdomen and legs are not uncommon. 
A large number of epitheliomata have been observed to 
arise in these burns; hence, it must be assumed, if the 
Cohnheim theory is valid, that in this particular tribe alone 
aberrant remains are present on the abdominal wall, since 
in other races such epitheliomata are unknown. There is, 
likewise, the fact that the Philippine and the Malay women 
who chew betel nut, and keep the masticated materials in 
the mouth overnight, develop epitheliomata at the point 
where this substance has been in contact with the mucous 
membrane of the cheeks;^ hence a special deposition of 
embryonic cells must be assumed in these people alone, for 
neoplasms in this region are rare in other races, which are 
not subject to such constant irritation of the part. 

The theory of an alteration in the tissue balance be- 
tween epithelium and connective tissue occurring only in 
old age does not explain the appearance of tumors in youth, 
nor, as has been said, of sarcomata, v. Hansemann has 
studied with great care the morphological variations of 
the chromatin and cell body in the cells of malignant 
growths, and thinks that the peculiar growth energy of 
tumor cells is due to the loss of the elaborate structure of 
the adult cell, with a return to a simpler form. The cell, 
therefore, can devote all its energy to growth and ceases 
to perform the highly specialized function which it has 
under normal conditions. Such changes may be produced, 
he thinks, by the unequal division of the cells which occurs 

^Davis: Jour. Am. Med. Assn., 1915, Ixiv, 711. 

20 



from multipolar mitoses. The weak point in this theory- 
is that such irregular mitoses may be found in benign 
tumors and even in regenerating normal tissues. 

Boveri has added a new phase to this hypothesis by 
suggesting that the irregular mitoses result in the produc- 
tion of a large series of abnormal cells, which, by the pro- 
cess of natural selection of the tissues, are destroyed if 
they are unequal to the conditions, or ultimately survive 
with powers to grow uninfluenced by the antibody or 
phagocytic activities which are early employed by the body 
in destroying foreign substances. These views Ribbert ob- 
jects to as assuming that all the changes are placed in 
the cell itself. He holds that isolation from the tissue or- 
ganization is a necessary condition for the origin of tumors, 
and that when this is accomplished the alterations in the 
cell are possible. These cells cannot be simply defective 
cells as assumed by Borst, for defective cells are less capable 
of growth than normal ones. Boveri's assumption that a 
pluripolar mitosis may by removing something from the 
cell make it capable of limitless proliferation is without 
foundation, as such division leads to imperfect cells less 
capable of growth. Even if such cells should have growth 
ability there is no evidence that anything but local hyper- 
plasia would result. Even normal cells have continuous 
growth capacity in culture. Any racial selection of cells 
is pure hypothesis. So far Ribbert.^ Morgan also holds 
that irregular mitoses only produce enfeebled cells. Rib- 
bert's own view is that the tumor cell does not differ in 
any respect from the normal cell and requires no new 
qualities except in its adaptability to unrestrained growth 
in the tissues. He points out the transplantability of 
normal tissue as an evidence of this point, and suggests 

^Ribbert: Naturwissenschaften, 1914, ii, 676. 

21 



that the reason why such transplants do not grow inde- 
finitely is that the cells have not yet had time to learn to 
grow and adapt themselves to the new surroundings which 
are always antagonistic. 

In his earlier papers, Ribbert stressed the inflammatory 
reaction of the connective tissue as the dominant factor in 
tumor production, but of late years he has shifted his atti- 
tude and now believes that there are primary changes in 
the epithelium as well. 

Adami^ has added to the theories of the origin of 
cancer one in which he assumes that the cell is acted upon 
by some external influence or influences which cause the 
change in its normal metabolic processes, with the result 
that in some way the habit of life of the cell is altered so 
that instead of performing its usual function, it ceases to 
be specialized and may becom.e merely a growing organism. 
This assumes the inheritance by the cell of acquired char- 
acters, and is merely a description of what may occur and 
does not offer any explanation of the underlying cause or 
causes of cancer. 

A further theory ascribes cancer to the action of some 
parasite which either causes irritation of the tissue in 
which the cancer arises, or invades the cell itself and causes 
it to proliferate. The majority of pathologists do not hold 
this theory ; but it is widely accepted by clinicians, although 
most of^the arguments adduced in support of it are without 
value. The statistical reports of the occurrence of cancer 
in certain districts, houses, etc., which are supposed to 
demonstrate the contagious nature of the disease, have long 
since been shown to be of little value. If there is one fact 
that we know about cancer, it is that it is not contagious. 
It is also certain that so far as our knowledge now extends 

^See, for an interesting discussion of this and cognate themes, 
Adami: Medical Contributions to the Study of Evolution, London, 1918, 
pp. 263-350. 

22 



the entrance of a parasite into a cell usually causes destruc- 
tion of the cell rather than its growth. Another argument 
is that the crushed tumor tissue of a mouse cannot produce 
a growing tumor, though this crushing would not destroy 
a bacterium of any type with which we are acquainted. 
The only known exception is the fowl tumor described by 
Rous.^ The long period of quiescence which may follow 
the removal of a primary malignant tumor only to be suc- 
ceeded in turn by rapid recurrence and generalization is 
difficult to explain if the cancer cell is supposed to contain 
a parasite which stimulates it to growth; and, also, the 
fact that tumors grow more rapidly in well nourished per- 
sons and do not always produce cachexia is against the 
parasitic theory. ^ 

Numerous organisms have been found in cancer, spiro- 
chetes, yeasts, bacteria of various types, but none of them 
have been shown to be capable of reproducing the tumor. 
Nevertheless, it is impossible to state that cancer is not 
due to some infectious agent of a type which must, how- 
ever, be entirely different from any with which we are now 
acquainted.^ 

The substance of all the theories on the causation of 
cancer may be summed up by saying that they consider 
the predisposition to cancer as the result of tissue displace- 
ments or of chronic irritation acting upon normal cells. A 
third factor generally acknowledged is the but little under- 
stood changes in the tissues which are comprehended under 
the term "age." For by far the largest number of tumors, 
both in man and in animals, affect those who have passed 

iRous: Jour. Exper. Med., 1912, xv, 119, 270: Jour. Am. Med. Assn., 
1912, Iviii, 1751, 1840. 

2Wells: The resistance of the human body to cancer, Jour. Am. Med. 
Assn., 1909, Hi, 1731. 

3See, for a full discussion of the various arguments for the parasitic 
theory, Emery: Tumors, Their Nature and Causation, London, 1918. 

23 



middle life.^ Nevertheless, it is perfectly obvious to those 
who are familiar with the experimental work in cancer and 
have studied the occurrence of human tumors, that mere 
tissue displacement or irritation or age is not a necessary 
factor in the production of cancer, since many persons have 
tissue displacements in which tumors do not arise, many 
suffer chronic irritation for long periods, even years, with- 
out the production of a tumor, and still others live to a 
green old age and escape a neoplasm. What this vital 
change in the tumor cell is which alters it so that it may 
grow without restraint in the body of the host is the cancer 
problem, and that has as yet escaped solution. 

HEREDITY AND CANCER 

That cancer can be transmitted directly from mother 
to child is most improbable, but that the liability to cancer 
is hereditary is certainly possible. For example, if tumors 
arise, according to the Cohnheim theory, in misplaced 
groups of cells, as is quite probable from our knowledge 
of some of the complex tumors of the body, it is perfectly 
proper to speak of such tumor liability as hereditary, be- 
cause in some instances these cell displacements occur in 
successive generations. Good examples are retinal neuro- 
epithelioma and fibroma molluscum. It is possible, also, in 

^As anxevidence of the statistical rubbish which is published on 
this subject, see Watzold (Ztschr. f. Krebsforsch., 1919, xvl, 318) who 
on the basis of 56 cases of cancer in patients under thirty-five occurring 
in his army experience holds that "it can no longer be maintained that 
cancer is a disease of ag-e," So experienced an investig-ator as Fibiger 
(Jour. Cancer Research, 1919, iv, 367) uses this statement to substan- 
tiate some arguments concerning the early appearance of cancer in 
rats. In this connection it is interesting to note that in the monograph 
on Mortality from Cancer, published by the Census Bureau, Washing- 
ton, 1916, the total deaths from "cancer and other malignant tumors" 
in the United States Registration Area during 1914 numbered 52,420, 
of which 2,570 were of persons under 35 years of age. Sarcoma and 
carcinoma are not separated in the census returns, but it is not likely 
that sarcoma caused more than one-tenth of the deaths from malignant 
tumors. See, also, for numerous instances of carcinomata in children, 
Merkel: Bruning and Schwalbe, Handb. d. allg. Path. u. path. Anat., 
Wiesbaden, 1912, i, 343. 

24 



certain families where the inbreeding has been very close 
that a general cancer liability may be produced; but that 
such liability exists to any degree in the whole population 
has been negatived by the investigations of the insurance 
actuaries, by whom it has been shown that a history of 
cancer in the ancestry of the insured makes that person 
no more susceptible to cancer than any other person in the 
normal population exposed to the disease. On the other 
hand, the experiments of Murray^ have shown that the 
introduction of breeding mice of cancerous ancestry into 
certain strains of these animals increased the number of 
spontaneous tumors appearing in the succeeding generations, 
the increased rate of occurrence being double the rate of 
occurrence in the offspring of normal mice. Such results 
cannot, however, be applied to man, as the experimentally 
produced concentration of cancerous ancestry is greater 
than could ever occur in the human race. Another point 
to be considered is that if cancer is hereditary the entire 
race should have been destroyed, because, as the disease 
afflicts chiefly persons after the reproductive age has been 
passed, it does not interfere with the increase in the popu- 
lation; and, hence, there should have been an increasingly 
greater concentration of cancer ancestry through the ages, 
with the result that the disease should be very much more 
abundant than it now is. Such concentration does not 
appear statistically in any known race, even though the 
inbreeding is fairly close so that the original stock is not 
much diluted by immigration. 

INCREASE IN CANCER 

There has been a great deal of discussion in recent 
years concerning the increased rate of occurrence of cancer. 

^Murray: Proc. Roy. Soc. Series C, 1911-12, Ixxxiv, 42. See, also, 
Slye, M.: Jour. Cancer Research, 1916, i, 479, 503; 1920, v, 53: and Tyzzer: 
Jour. Med. Research, 1907-08. N. S. xii, 199. 

25 



One school of statistical research holds ''that the mortality 
of cancer is increasing at a more or less alarming rate 
throughout the entire civilized world, and that this increase 
implies most serious consequences, present and future, to 
the population concerned."^ 

Another group of statisticians holds that "the reported 
mortality from cancer is increasing in almost every part 
of the world, but the real mortality, if increasing at all, 
is certainly not increasing with equal rapidity. . . . 
In England and the United States the increase in cancer 
mortality is parallel with the increase in mortality from 
appendicitis, and both may be due entirely, as they certainly 
are in large degree, to the improvement of diagnosis. . . 
. . The cumulative evidence that improvements in diag- 
nosis and changes in age composition explain away more 
than half and perhaps all of the apparent increase in cancer 
mortality rebuts the presumption raised by the figures, 
and makes it probable, although far from certain, that 
cancer mortality is not increasing."^ 

TRAUMATIC ORIGIN OF TUMORS 

The belief in the relationship between injury and the 
occurrence of tumors is widely held by the laity, and is also 
adhered to by many physicians.^ The basis for it, however, 

iHoffman, F. L.: The Mortality from Cancer Throug-hout the World, 
Newark, N. J., 1915, p. 218. 

^Willcox, W. F. : On the alleged increase of cancer, Jour. Cancer 
Research, 1917, ii, 267. See, also, Dublin, L. I.: Mortality Statistics of 
Insured Wage Earners and Their Families, Jour. Cancer Research, 
1919, iv, 235; and Newsholnve: Elements of Vital Statistics, London, 
1899, p. 2-41. 

sColey, W. B.: Ann. Surg., 1911, liii, 449; Lowenstein, Unfall und 
Krebskrankheit, Tubingen, 1910, give a general collection of cases with no 
attempt at analysis. Graef, W.: Centralbl. f. d. Grenzgeb. d. Med. u. 
Chir., 1913, xvii, 603, gives the best critical review with bibliography. 
See, also, Stern: Traumatische Entstehung innerer Krankheiten, 1913, 
p. 487; Ribbert: Geschwulstlehre, 2d ed., Bonn, 1914, pp. 101, 299; which 
both give fairly complete bibliographies; and Engel, Die Beurteilung 
von Unfallfolgen, Berlin, 1913, p. 340. 

26 



is largely superficial or incorrect observation. It is almost 
impossible, for example, to take the history of a patient 
suffering with carcinoma of the breast without being able 
to link the appearance of the tumor, at least in the suf- 
ferer's mind, with a history of trauma to the organ. In 
the literature of the subject, also, there are many instances, 
gravely cited as proving a correlation between trauma and 
cancer, in which the injury had occurred at a period of one 
week to two months before the appearance of the tumor, 
although what we know of the growth rates of neoplasms 
of the breast proves that it is utterly impossible that a 
tumor should during that period have reached the size 
frequently found. The same is true of many of the sar- 
comata of the long bones, which are currently supposed to 
appear after fracture. The growth rate of such tumors is 
slow, as a rule, and careful study of the history and exami- 
nation of the tissues of the region will show that they have 
evidently existed for a long period previous to the occur- 
rence of the fracture, which makes its appearance at the 
site of the neoplasm simply on account of the softening 
and erosion of the bone by the growth of the tumor itself. 
The results of animal experimentation have shown that it 
is impossible, even in a strain of mice which are highly 
susceptible to tumor production as shown by spontaneous 
occurrence, to produce a tumor by a single trauma. In 
fact, irritation for six months or even a year with chemical 
substances which seem to incite cancer in man will in mice 
be followed by only an occasional neoplasm. While we may 
be certain, therefore, that a single blow does not cause a 
tumor, it is, on the other hand, possible that long continued 
irritation following injury may give rise to tumor forma- 
tion. But even long continued irritation is not necessarily 
correlated with the appearance of the tumor. The great 
frequency with which crural ulcers from varicose veins are 
seen in the dispensary population in any large city gives 

27 



some idea of the number of people in the world carrying 
these lesions, and yet with all these persons suffering from 
a source of chronic irritation and ulceration, the instances 
of carcinomata ultimately developing in such ulcers are ex- 
tremely few. Scarcely a hundred cases have yet been re- 
ported in surgical literature. If the cases of tumors which 
have been merely reported as caused by trauma are col- 
lected, it will be found that there are not over a thousand 
which will bear the slightest inspection, much less are cer- 
tain; and yet some 500,000 people die annually of cancer. 
If we also stop to realize how many individuals receive 
repeated blows in various portions of the body and how 
many fractures of the limbs occur without the production 
of a sarcoma at the site of fracture, the statistical evidence 
is strong that there can be no necessary correlation between 
a blow and the production of a tumor ; and that any connec- 
tion in time is merely an accidental coincidence of two 
wholly independent events. It would rather be expected, on 
the contrary, that an injury which causes severe destruc- 
tion of tissue instead of producing a neoplasm would pro- 
duce regenerative phenomena solely. Nevertheless, there 
is always the possibility that there exists a certain amount 
of displacement of epithelial cells, for example, into the 
deeper tissues ; but even when this occurs we find that these 
displaced cells produce, so far as the records show, only 
dermoid cysts rather than neoplasms. Such epidermoid 
cysts are frequently found on the hands of laborers, and 
especially on the fingers of seamstresses, the epithelial 
cells being transplanted into the corium by puncture of 
the needle. There is no record that such an epidermoid 
cyst ever became malignant, and thousands of similar im- 
plantations of adult and fetal material have been made 
experimentally without the production of a cancer. Re- 
peated trauma of tendons, aponeuroses, or any connective 
tissue may cause necrosis, calcification, and often bone 

28 



formation; but the tumor so produced is inflammatory or 
hyperplastic, and is not a true neoplasm. 

While it may be safely assumed, therefore, that a single 
trauma never causes a tumor, it is, however, always theore- 
tically possible, though as yet not proved, that trauma may 
hasten the growth of a tumor already under way, possibly 
by increasing the vascularity and hence the amount of food 
brought to the part. On the other hand, it has been repeat- 
edly observed that a moderate trauma applied to a tumor 
may cause rupture of the thin-walled capillaries, hemor- 
rhage, destruction of a considerable portion of the tumor by 
necrosis owing to lack of blood supply to the part, and 
actually a very considerable reduction in the size of the 
mass, thereby decreasing instead of increasing its growth, 
so that even stimulation by trauma must not be assumed 
without careful microscopic study of the individual tumor 
for evidence of rapid growth. Untreated tumors often 
show astonishing fluctuations in growth rates even from 
month to month. 

Quite another phase of the trauma question appears 
when injury causes a growth such as a keloid, which is 
more an hypertrophy than a true tumor, or when the injury 
is of a chronic type, such as the continuous rubbing by 
the clothes of a pigmented mole, which may ultimately un- 
der this process supposedly gain qualities which are termed 
malignant, or when, after a severe burn, a sarcoma or a 
carcinoma has, as in a very few instances, afterward devel- 
oped in the scar tissue. The Roentgen-ray carcinomata 
belong in this class, though strictly they are caused not by 
the rays, but by the incurable inflammation which follows 
their improper use.^ After exposure to Roentgen rays over 
a long period, a chronic dermatitis is produced which in a 
certain number of persons of the cancer age, say forty to 

^Wolbach: Jour. Med. Research, 1909, N. S. xvi, 415. 

29 



forty-five, may go on to the development of a carcinoma, 
although such production is very rare as compared v^ith 
the number of persons burned, and depends apparently on 
the individual. Similar relationships are shown in the car- 
cinomata of brass workers, of men working with coal tar,^ 
and of those using large quantities of arsenic for long 
periods,^ and in other types of irritation new growth, includ- 
ing the kangri cancers and the epitheliomata of the inner 
surface of the cheek following chewing of the betel nut. 
All of these influences, however, are chronic. They tend 
to set up inflammatory lesions; they disturb the relation- 
ship between the epithelium and the connective tissue; 
and, what is more important than anything else, they do 
not result in a tumor in every person who is afflicted by 
such a lesion; in other words, behind the production of a 
carcinoma lies some other factor which we do not know. 
The same phenomenon is observed in animals. It has been 
possible by treating many hundreds of rats with burning 
doses of Roentgen-rays to produce in two instances only 
a carcinoma and a sarcoma.^ Epitheliomata of the skin of 
rabbits and mice have been produced by painting the sur- 
face with coal tar for a long period. Fibiger* has shown 
that the presence of spiroptera in the gastric mucous mem- 
brane of certain rats may incite the growth of a true neo- 
plasm, though usually it produces merely a hyperplasia. It 
has also been shown that the presence of the cysticercus of 
Tenia crassicola in the liver of rats may incite the growth 
of a sarcoma in the cyst wall.^ The most plausible explana- 
tion of the connection between the appearance of carcinoma 

iDavis, B. P.: (chemical cancer) Jour. Am. Med. Assn.. 1914 Ixii 
1716 (bi,bl.);Le&ge: Special Report on Ulcer of the Skin and Epithelial 
Cancer in the Manufacture of Patent Fuel, Home Office Pub., London. 
2Pye-Smith: Lancet, 1913, i, 1313. 
^Clunet: Recherche experimentelle sur les tumores malignes, Paris, 

■^Pibiger: Jour. Cancer Research, 1919, iv, 367 (bibl.). 
'Bullock and Rohdenburg: Jour. Cancer Research, 1916, 1, 87. 

30 



and chronic irritation of all sorts is that by such chronic 
processes the epithelial cells are separated from their nor- 
mal relations with the deeper connective tissue, and thus 
are enabled to learn, in some fashion which we do not 
understand, to grow continuously without interruption from 
the normal controlling processes which keep the structures 
of the body in their usual position. Obviously, this explana- 
tion is merely one of words only ; we do not know the ulti- 
mate underlying reason for tlie change in the nature of an 
epithelial cell which makes it under one circumstance a part 
of the normal covering of the body, and under another a 
portion of a widely growing, destructive tissue. 



CHEMISTRY OF TUMOES 

In recent years a large number of investigations has 
been made on the composition of tumor cells, in the attempt 
to discover some chemical differences between the cells of 
a neoplasm and those of normal homologous tissue, and 
while final conclusions have not been reached, the general 
opinion is that if strictly comparable analyses are made no 
important differences in chemical composition can be 
demonstrated. It is, for example, incorrect to compare 
rapidly growing masses of epithelium, such as occur in 
cancer of the breast, with normal breast structures as a 
control, first, because the latter are not growing rapidly, 
and second, because they are not largely composed of 
epithelium. Even the cells of a liver carcinoma would not 
be strictly comparable to those of the quiescent, normally 
functioning liver. It is far more reasonable to assume, on 
the contrary, that tumor cells do not vary greatly from 
the norm in chemical composition, for the reason that they 
produce metabolic products identical with those of the cells 
from which they arose. Thus, as is stated in the section on 

31 



metastasis, liver carcinoma produces bile; thyroid carci- 
noma produces thyroid material ; pigmented tumors produce 
the same melanin which is present in the quiescent pig- 
mented mole from which they originated. So, also, it seems 
doubtful that in the origination of the tumor the few cells 
from which the mass starts could differ to any great degree 
from the normal cells of the body, since if they did they 
would of necessity act as foreign bodies and incite prompt 
immunity reactions of some type — cytolytic, phagocytic, 
etc. The fact that tumors do arise so frequently points 
rather to the other assumption, that they differ little, if at 
all, from the surrounding homologous cells. We may, there- 
fore, safely conclude, until much more concordant chemical 
studies have been completed, that the metabolism of the 
cancer cell does not to any extent differ from rapidly grow- 
ing cells of the same type.^ 

IMMUNITY IN CANCER 

The idea that immune processes of a type comparable 
to those active in the bacterial infections of man might also 
exist in connection with malignant tumors has long been 
current. The basis for the theory was the occasional oc- 
currence of spontaneous disappearance of neoplasms, either 
following infection, especially with the streptococcus, or 
subsequent to slight operative procedures, or even without 
any outside interference at all. The facts were loosely 
coupled with the assumption that these disappearances 
must be due to immunity. 

1. The argument that immunity to cancer exists was 
strengthened in the minds of those favorably inclined by 
the observation that implanted tumors in mice and rats 

«. ^The very large literature of the subject will be found In Neubere- 
Ztschr. f Krebsforsch 1910, x 55; Blumenthal; Asher-Splro. E?glbm 
d. Physiol., 1910, x, 363; von Furth: Probleme d. physiol u oath 
Phfladelphiirlfis'^'^' ^' ^^^' ^""^ ^^"'' ^- ^'' CJ^emical Patiiofo^S; 

S2 



may regress, often leaving the animal resistant to further 
implantation. The fact was overlooked that implanted 
tumors and spontaneous tumors are not comparable and 
that regression in spontaneous tumors is as rare in mice 
as in man. 

2. The production of resistance to transplantation 
after injection of homologous tissue, also, led to the hope 
that immunity to tumor growth might be obtained. 

3. Additional confusion was produced by the loose 
transference of ideas of bacterial immunity to the hypo- 
thetical immunity in cancer, for it was not realized that in 
one case the cell is a foreign parasite, while in the other it 
is native to the host which carries it. 

These three notions have led to extensive series of ex- 
periments, with heated cultures of bacteria, bacterial 
toxins, human blood serum from infants and adults, ex- 
tracts or emulsions or implantations of fetal or adult tissue, 
vaccines of ground cancer tissue, either autologous or 
heterologous, tissue autolysates, and, finally, immune sera 
prepared by treating animals with cancer tissue. All these 
forms of treatment are without the slightest effect on the 
progressive growth of malignant tumors, though the failure 
to produce specific organ cytotoxins might have prepared 
us for the failure of cancer cytotoxins. 

A second phase of research for a cancer immunity was 
based upon the study of the morphological changes occur- 
ring in a suitable host, which showed that the process is 
often, though not always, accompanied by the collection of 
a lymphocytic exudate surrounding the graft, such as has 
long been observed about slow-growing human tumors. 

The first and most obvious step was to attempt by the 
injection of large amounts of lymphoid tissue to influence 
the tumor growth.^ A number of discordant reports exists 

^Theilhaber: Die Entstehung- und Behandlung der Karzinome, Berlin, 
1914; Ribbert: Deutsch. med. Wchnschr., 1916, xlii, 278; Kaminer and 
Morgenstern: Wien. klin. Wchnschr., 1917, xxx, 41. 

33 



in the literature, but the repetition of the experiments at 
the Crocker Fund laboratory on a scale large enough to 
remove experimental fluctuations has shown that no effect 
is observable. Neither is the reverse true, that excision 
of the spleen, an important lymphoid organ in mice, facili- 
tates tumor growth. 

Inasmuch as bleeding has been shown to stimulate the 
production of immune antibodies, and even of autologous 
immune substances, such as agglutinins,^ attempts have 
been made to stimulate by this procedure the normal re- 
sisting power of animals and even of human beings to 
tumor growth. This has, however, been without effect, a 
result which might have been expected, since it was shown 
some time ago that the injection of autologous tissue pro- 
duced not only no immunity to cancer growth,^ but none 
even to transplantation.^ 

It has been suggested, from morphological studies 
alone,* that possibly the lymphocytes and plasma cells may 
be carriers of immune substances, inasmuch as they collect 
about regressing tumors. Stress has been laid, also, on the 
destruction of transplanted normal tissues by increased 
activity of the small mononuclear cells,^ and this view has 
been upheld by others.^ In this connection, however, the 
fact that lymphocytes in man collect chiefly about slow- 
growing tumors and not about the highly malignant forms, 
together with the additional fact that metastases are fre- 
quent in lym.ph-nodes, has not been given sufficient weight. 

To test this question the following work has been done 
at the Crocker Fund: 

iRoDertson and Rous: Jour. Exper. Med., 1918, xxvii, 563. 

2Haaland: Jour. Path, and Bacteriol., 1910, xiv, 407. 

sWoglom: Ztschr. f. Immunitatsforsch. u. exper. Therap., Grig.. 1911. 
xi, 683. 

*Da Fano: Ztschr. f. Immunitatsforsch. u. exper. Therap., Grig-., 
1910, V, 1. 

^Loeb, Li.: Jour. Am. Med. Assn., 1915, Ixiv, 726. 

«Murphy, J. B., and Taylor, H. D., Jour. Exper. Med., 1918, xxviii, 1. 

34 



In the first place, preliminary investigations of the 
blood of white rats and mice showed that great caution 
must be exerted in considering any particular count a norm. 
One hundred per cent, fluctuations from day to day or from 
week to week were not infrequent, and great differences in 
cell-type percentages also were observed; the radiation 
effects on the lymphocyte counts are, also, very variable. 

1. Assuming that the lymphocytes carry protective 
substances, mice with lymphatic leukemia or very high 
leukocyte counts, 20,000 to 30,000, should show some im- 
munity to tumors. This is not the case. Other investi- 
gators have not been able to show that an artificial lympho- 
cytosis had any effect on tumor growth.^ 

2. If grafts of normal tissues such as tl^yroid are de- 
stroyed by lymphocytes, a preliminary reduction of the 
total leukocyte count, especially by means of x-rays or 
radium, should result in a greater number of takes. This 
we have not been able to demonstrate, even when many 
hundreds of grafted animals and controls were used. 

3. In this same connection it was important to de- 
termine whether a tumor of very low growth-potentiality 
could be influenced by the destruction of the lymphocytes. 
Such a tumor is a guinea-pig fibrosarcoma, the percentage 
of takes of which is very small. The animals were 
x-rayed previous to and following the inoculation of the 
tumor, the site of the growth being protected by lead. No 
increase in the number of takes was observed. An immune 
strain of rats was obtained and rayed, and tumors then 
inoculated; but no change in susceptibility was noted. 

4. The effect of the reduction of the lymphocytes in 
the circulating blood on the rate of take of tumors was 
studied, first with transplanted tumors, secondly with pri- 
mary tumors inoculated into a series of animals, half of 

^Sittenfield, M. J.: Jour. Cancer Research, 1917, li, 151; Jour. Med. 
Research, 1918, N. S. xxxiii, 465. 

35 



which were rayed, the raying being either very light or 
very heavy. Not the slightest difference could be observed 
over a considerable series of experiments between the rayed 
and the not-rayed animals. 

5. Finally, the raying of rats in which a highly viru- 
lent m.ouse tumor had been implanted did not prolong the 
life of the tumor. 

It is, therefore, evident that the lymphocyte is in no 
way correlated with cancer immunity. 

Inasmuch as all the serological reactions — precipitins, 
agglutinins, and complem.ent-fixation — are not produced in 
either human or animal hosts bearing the tumors, it is plain 
that it is impossible to speak at present of a true immunity 
to cancer. All we know is that an immunity to implanta- 
tion from one animal to another can be produced. If this 
immunity could be extended so that it v/ould be possible 
to prevent the implantation of turners of the host in his 
ov/n body, an important advance v/ould be made in the 
therapeutics of cancer, because this would check metastasis. 
But even this point has not as yet been reached. 



SPONTANEOUS DISAPPEARANCE OF TUMORS 

In a very small proportion of human malignant tumors, 
spontaneous disappearance for longer or shorter periods has 
been noted. The greatest number of such disappearances 
has followed incomplete surgical removal of the tumor; 
they have occurred next in order of frequency during some 
acute febrile process, and least frequently in connection 
v/ith some profound alteration of the metabolic processes 
of the organism, such as extreme cachexia, artificial meno- 
pause, or the puerperium. The cause or causes of such 
spontaneous disappearances are, however, not at all under- 
stood. As has been stated in the section on Immunity, no 

36 



evidence of any immune process has been demonstrable. 
Unquestionably, in some instances, interference with the 
circulation of the tumor has played some part. High tem- 
perature alone will not cause tumors to regress, as has been 
amply demonstrated by the injection of streptococcus 
toxin, nor will simple starvation effect the absorption of 
the tumor.^ In many instances, at a period of from one to 
five years, after partial or complete disappearance of the 
tumxor, recurrence has taken place in the internal organs, 
thus showing that not the whole growth, but only the por- 
tions which were accessible to physical examination, had 
ceased to grow. 

The frequency of such disappearance cannot be ac- 
curately estimated. Bashford has stated that it occurs 
probably in approximately one case in 100,000, but only 
som.e 300 well verified instances can be found in the litera- 
ture of the subject.^ 

MULTIPLE PRIMARY NEOPLASMS 

The occurrence of multiple primary tumors has been 
often observed in man; in one autopsy series 3 per cent, 
of all persons dying of cancer had multiple malignant 
growths.^ They also occur with considerable frequency in 
animals,^ especially in the mammary carcinomata of mice. 
In man the tumors frequently have very differing biological 
qualities, for example, the writer has seen an epithelioma 
of the lip which remained fairly localized and was success- 
fully removed by operation with no recurrence at the end 

iJaworski: Wien. klin. Wchnschr., 1916, xxix, 1646. 

^Rohdenburg: Fluctuations in the growth energy of malignant 
tumors in man, with especial reference to spontaneous recession, Jour. 
Cancer Research, 1918, ill, 193. 

^Harbitz, F.: Norsk Mag. f. Laegevidensk, 1916, Ixxvii, 181. Abst. 
in Jour. Am. Med. Assn., 1916, Ixvl, 994. 

^Goodpasture and V/islocki: Multiple Tumors in Dogs, Jour. Med. 
Research, 1915-16, N. S., xxviii, 455. 

37 



of a year. By this time, however, a very large carcinoma 
of the thyroid developed involving all the lymph-nodes of 
the neck with such extensive invasion of the surrounding 
tissues that it was inoperable and resulted in the death of 
the patient in a few months. At autopsy no trace of the 
squamous-cell epithelioma of the lip could be found in the 
regional lymph-nodes adjoining that part of the face, while 
numerous metastases from the carcinoma of the thyroid 
were present. Woglom^ has shown also that in mice mul- 
tiple tumors developing in the mammary glands, although 
having similar morphology, may possess either the same 
adaptability to inoculation or very differing qualities, thus 
demonstrating that similar tumors arising coincidently in 
the same animal are by no means biologically equal. Other 
examples from human pathology are not infrequent. In- 
stances are reported of basal-cell tumors of the face com- 
bined with carcinoma of the stomach, intestines, or breast. 
As is well known the basal-cell tumors hardly ever meta- 
stasize, whereas the carcinomata are extremely malignant. 
Not only may multiple tumors appear in various portions 
of the body, but two or more tumors may develop from 
the same origin ; for instance, the writer has seen a car- 
cinoma of the breast in which two types were present, both 
metastasizing into the axillary lymph-nodes as discrete, 
separate nodules of distinct histological type. That tumors 
of the skin of the face are frequently multiple is well 
known, and neoplasms arising on the basis of irritation 
from tar or the Roentgen rays are also frequently multiple. 
The same is true of carcinoma of the intestines arising on 
the basis of multiple congenital polyps. While the diagnosis 
of multiplicity in cases of synchronous carcinomata of the 

^Wofflom: Virulence or Adaptation. Jour. Cancer Research, 1919, 
iv. 1. 

38 



skin, which Borrmann^ places at about 22 per cent., is not 
difficult, a certain discretion is necessary in applying the 
name "multiple tumors" to neoplasms arising in the same 
organ. Only careful microscopical examination of the 
tumor will prevent an erroneous assumption in failure to 
diiferentiate between two independent primary tumors and 
multiple neoplasms, based either upon local extension or 
produced by a metastasis from a small, slow-growing, pri- 
mary tumor giving rise to a larger metastatic deposit. The 
importance of such study was long unrecognized in con- 
nection with the bilateral ovarian tumors of the type which 
bears the name of Krukenberg.^ These tumors were con- 
sidered as primary in the two ovaries, but recently it has 
been shown that they are instead primary in some portion 
of the gastrointestinal tract or gall-bladder, and that the 
ovaries are involved only secondarily by metastasis. 

When the tumors originate upon the basis of some con- 
genital deformity, such as the polypoid growths of the in- 
testine, or are connected with other defects, as are the 
sebaceous adenomata of the face with tuberous cerebral 
sclerosis, it is not difficult to understand how they may 
frequently be multiple. When the malignant change follows 
long continued chronic irritation over a large area the 
tumors are also likely to be multiple. The carcinomata of 
the skin, for instance, are due to a similar chronic irrita- 
tion acting upon the epidermis of the face, but the presence 
of a carcinoma of the uterus and of a carcinoma of the 
stomach must be based upon different irritants. In general, 
it seems probable that the tissues of the body of such per- 
sons are much more susceptible to the development of 
cancer than those of the ordinary individual. When, there- 
fore, a suitable irritant, for example, a chronic gastric 

'Borrmann: Deutsch. Ztschr. f. Chir., 1905, Ixxvi, 404; also Ztschr. f. 
Krebsforsch., 1904. ii. 1. 

^Major, R. H.: Surg., Gynec, and Obst., 1918, xxvii, 195 (bibl.). 

39 



ulcer, is applied for a considerable time to the mucous 
membrane of the stomach, a carcinoma is much more apt 
to develop in such a susceptible person than in other in- 
dividuals perhaps of the same race and age. Similarly- 
some writers consider irritation to be a source of carcinoma 
of the uterus. Instances of such increased susceptibility 
have been observed in those who years before have had a 
successful operation for the removal of a neoplasm. One 
such example in the writer's experience was that of a 
woman who had had a carcinoma of the breast removed 
with success and ten years later developed a carcinoma of 
the uterus, so that any metastatic connection between the 
tumors could be ruled out. 

A combination of two types of carcinoma is much more 
frequent than that of carcinoma and sarcoma. Some in- 
stances, however, are recorded in which tumors of these 
two varieties have appeared, even in the same organ. 
Especially is this true of the uterus. The probability of 
the co-existence of two such growths is much less than 
that of the occurrence of two carcinomata, for sarcoma is 
at least ten times as infrequent as carcinoma. 

A very unusual form is a tumor composed of an inti- 
mate mixture of carcinoma and sarcoma. These tumors 
are exceedingly rare in man, only about forty-five cases 
being recorded.^ Most of them are in the uterus or esopha- 
gus, but instances have been reported in the ovary, the 
thyroid, the testicle, the brain, the stomach, and the gall- 
bladder, and also one in the pancreas and one in the liver. 
Interest in this type of tumor was renewed in recent years 

^Herxheimer: Zieglers Beitrage, 1908, xliv, 150. Lippraann: Ztschr. 
f. Krebsforsch., 1905, iii, 293. 

40 



after the discovery by Ehrlich^ and others^ that certain 
carcinomata in mice when transplanted and allowed to re- 
main in the animal for a sufficient period of time gave 
rise to a sarcomatous change in the connective tissue 
stroma. Haaland^ showed that the sarcoma and carcinoma 
could be separated either by mechanical means, such as 
shaking fresh sections of the tumor so that the carcinoma 
cell nests remained in the suspending fluid, or by heating 
the tumor to 44° C. for 35 minutes or more, the carcinoma 
being killed first; and that the two forms of neoplasms 
could grow separately and remain as different types 
through a number of series of transplantations. The car- 
cinoma, however, may retain the power of transforming 
connective tissue into sarcoma even after it has been cul- 
tivated for some generations. A recent paper by Woglom* 
reviews the subject to date. 

METASTASIS 

By metastasis is meant the distribution of tumor 
particles throughout the body, either by the blood or by 
the lymph-channels, resulting in the formation of secondary 
tumors. In general, metastasis is a property of malignant 
tumors only, but it may occur with growths which are be- 
nign, though never with the same frequency or to the same 
extent as with the truly malignant forms. ^ The recent 
extensive experiments on transplantation of tissues both 
in man and in animals have shown how metastasis of 

lEhrlich and Apolant: Berl. klin. Wchnschr., 1905, xlii, 873. Ehrlich: 
Ztschr. f. Krebsforsch., 1907, v, 62. 

^Bashford, Murray and Haaland: Berl. klin. Wchnschr,, 1907, xliv, 
1238. 

^Haaland: Berl. klin. Wchnschr., 1906, xliii, 40. 

*Woglom: Jour. Cancer Research, 1919, ii, 371. 

^Loeb and Fleisher: Transplantation of benign tumors, Jour. Cancer 
Research, 1916, i, 427. 

41 



normal structures may be possible. Transplantation of 
epidermis, of subcutaneous tissue, of periosteum, or even 
of the thyroid gland is quite possible if the tissue is trans- 
ferred to the body of the person from whom it was de- 
rived.^ Transplantation from one individual to another is 
usually only temporarily successful, and the graft as a 
rule disappears. The reason why the phenomenon is so 
infrequent in benign neoplasms is that the conditions for 
the entry of portions of the tumor into the vessels are not 
often fulfilled, inasmuch as benign new growths are usually 
encapsulated and do not invade the surrounding tissues in 
an infiltrative fashion. Instances have been reported, how- 
ever, in which apparently perfectly normal thyroid gland 
tissue has been found at a considerable distance from the 
original organ.^ Some of the very cellular angiomata, also, 
have been noted to grow out through the neighboring 
tissues and occasionally to form metastatic nodules at a 
distance.^ In general, however, the capacity to metastasize 
is confined to malignant tumors, the reason being that such 
tumors invade the walls of the lymphatics and the blood- 
vessels at a very early stage in their growth; and as a 
result there are free in these channels small masses of 
cells which, for example, are carried by the lymph to the 
nearest lymph-node, and there give rise to new tumors of a 
morphology similar to that of the parent growth. 

Mechanism of Metastasis 

There is still a good deal of discussion as to the 
mechanism of the transportation of tumor cells about the 
body, and some difference of opinion exists as to the rela- 

iManley and Marine: Jour. Am. Med. Assn., 1916, Ixvii, 260. 

^Gierke: Virchows Archiv, 1902, clxx, 464. 

3Borrmann: Zieglers Beitr., 1906, xl. 372; Jores: Centralbl. f. allg-. 
Path., 1908. xix, 662; Shennan: Jour. Path, and Bacteriol., 1914-1915. 
xix, 139. 

42 



tive importance of the different factors, though none as 
to the final results. For example, surgical opinion in 
America is strongly against diagnostic incision into tumors 
as facilitating the spread of the disease. This attitude is 
largely based on individual experience with a limited num- 
ber of cases. German surgeons, on the other hand, recom- 
mend the procedure when a diagnosis can be made in no 
other way. Experimental tests on animals show that a 
clean incision into a tumor does not increase the number 
of metastases.^ Hence it is evident that much more work 
must be done in collecting accurate statistics if the surgical 
attitude is to be maintained, for an early diagnosis is vital 
in the successful treatment of cancer and justifies the as- 
sumption of a moderate risk if certainty can be obtained 
thereby. Practically, the need of such diagnostic incision 
exists in only a moderate number of cases, and indiscrimi- 
nate cutting into tumors which can be diagnosticated 
clinically is to be deprecated. 

The general principles of metastasis are that cells or 
masses of cells which are set free in the lumen of the blood- 
vessels are quite frequently swept into the lung or through 
the portal system into the liver, and remain there, or, in 
the case of the lung, pass through the capillaries of that 
organ and are carried through the heart into the general 
circulation, thus being deposited in many, or all, of the 
organs of the body. Such capillary penetration takes place 
very early in many of the sarcomata, owing to the very 
close relationship which the cells of the tumor have with 
the delicately walled capillaries of the growth, so that in 
many instances the lungs are filled with metastatic nodules 
at a time when the diagnosis of the nature of the original 
tumor can hardly be made from the clinical appearance. 
In carcinoma, on the other hand, invasion of the vessel 

^Wood: Jour. Am. Med. Assn., 1919, Ixxiii, 764. 

43 



wall is rather a late phenomenon, though in individual in- 
stances, depending entirely on the accidental presence of a 
large vessel in or near the tumor or on the traumatic rup- 
ture of a vessel, distribution of the tumor material into the 
circulation may occur early. 

While most of the carcinomata when they grow 
through the wall of the vein set free individual cells or 
small masses of cells, certain types of tumors are apt to 
invade the lumen of vessels en masse. Tumors of this 
class are the hypernephromata of the kidney, the chorion- 
epitheliomata of the uterus, and, more rarely, other 
varieties. It is quite usual to see a hypernephroma of the 
kidney involve the renal vein and grow out into the in- 
ferior vena cava. Instances have been recorded in which 
this growth extended into the right side of the heart and 
even into the pulmonary artery. In one reported case^ a 
tumor of the left testicle, described as a lymphendothelioma 
but probably teratoid in origin, grew into the spermatic 
vein, the left renal vein, and the iliac vein, and, finally, 
through the vena cava into the right auricle. From this 
cavity masses passed to the pulmonary artery and invaded 
the lung, and from the lungs tertiary metastases invaded 
the other organs of the body. 

These intravascular masses are not composed wholly 
of tumor cells. The large proportion of the bulk is not 
infrequently made up of clot containing a variable amount 
of red and white blood-cells and fibrin. 

Obviously, those tumors which early invade the vas- 
cular system are most apt to form metastases in different 
organs. The hypernephromata, for example, frequently 
make their appearance in the bone marrow before the pri- 
mary tumor has given any symptoms; and attention may 
be called to the metastases by spontaneous fractures or 

iMacCallum: Bull. Johns Hopkins Hospital, 1900, ix, 497. 

44 



by softening or rarefaction of the bone or by some sub- 
periosteal neoplasm, and the nature of the primary growth 
be revealed only by microscopic examination of the second- 
ary nodule. The writer has seen a single subcutaneous 
metastasis on the skin of the arm from a hypernephroma 
of the kidney, no other being found even on autopsy. 

Another and somewhat infrequent route for the in- 
vasion of the blood-vessels is by way of the thoracic duct. 
This is taken obviously only by tumors of the abdomen or 
thorax which lie in proximity to the thoracic duct, or in- 
vade lymph-channels leading directly to it. The particles 
thus set free enter the venous circulation and are carried 
to the lung, or, passing through the capillaries of that 
organ, fall into the general circulation and are deposited 
in the different portions of the body. 

Even after tumor particles have entered the circula- 
tion and have been generally distributed, there are con- 
nected with the ultimate growth of metastases a number 
of interesting phenomena, about which there has been 
much confusion. It is a well known clinical fact that metas- 
tasis is extremely rare in muscular tissues, and the ex- 
planation for this must be looked for in the mechanical 
conditions which exist in these organs. When, for example, 
the cancer cell is deposited in a small capillary in the car- 
diac muscle, if it is not already surrounded by fibrin and 
a few agglutinated leucocytes it quickly gains such a cover- 
ing. Here it forms a minute embolus which by the con- 
traction of the muscle is continuously in motion, and it is, 
therefore, unable to attach itself to the vessel wall and 
obtain the vascularization and connective tissue stroma 
which is necessary for the ultimate continuous propagation 
of the neoplastic cells. For this reason, metastases are 
extraordinarily rare in the muscle substance of the heart, 
and though more frequently seen, are also rare in the 

45 



epicardium or pericardium. The same mechanical condi- 
tions apply to the voluntary muscles of the body. Metas- 
tases in the muscles are extremely rare if we except some 
of the sarcomata which spread through the muscle tissue 
itself by direct extension from the primary tumor. Even 
the pectoralis muscles show but little invasion except by 
extension directly from the breast, unless the tumor has 
been massaged. Details of this phase of metastasis can 
be easily studied by experimental means. If a mouse 
tumor is massaged, especially a tumor with small size cells, 
the lungs of the animal will be found in a few days riddled 
with small thrombi of one to usually not more than ten 
tumor cells surrounded by leucocytes and fibrin. A few 
only of these masses begin to invade the vessel wall and 
form vascular connections at this time. In the control 
animals whose tumor has not been massaged, no such flood- 
ing of the pulmonary vessels is seen. If a series of mice 
whose tumors have been massaged and whose lungs pre- 
sumably contain these emboli are allowed to remain for 
two to six weeks so that the tumors may have a chance 
to grow, and are then autopsied, their lungs will be found 
to contain, as a rule, only a moderate number of metas- 
tatic growths, showing that only a small percentage of the 
emboli actually succeed in permanently establishing them- 
selves in this organ, which is of course continuously in 
motion with each respiration. The histological consistency 
of the tumor plays an important part in this mechanical 
distribution, for if a spindle-cell sarcoma is massaged, it 
will be found that it is extremely difficult to dislodge tumor 
particles into the circulation, the connective-tissue cells be- 
ing firmly united by their collagenous extensions, and not, 
therefore, easily set free in the circulation. Small-cell car- 
cinomata or sarcomata, on the other hand, can be diffused 
through the bodies of the experimental animal by mas- 
sage for a few moments only, with the exertion of such 

46 



pressure as will not cause noticeable hemorrhage into the 
tumor, in other words, such pressure as in human beings 
would give rise to very little discomfort. These experi- 
ments point very conclusively to one practical phase in the 
treatment of tumors, and that is that the patient should 
be warned under no circumstances to massage or rub the 
tumor after its discovery, and the surgeon should avoid 
all unnecessary manipulation, either in diagnosis or in 
operative procedure.^ 

Another metastatic phenomenon which is of interest, 
showing the mechanical distribution of tumor particles, is 
that in the brain the left side shows a very much larger 
proportion of metastases than does the right. The explana- 
tion is not that the left side of the brain is more suscepti- 
ble to tumor growth, but rather that the circulation on the 
left side of the brain is much greater than that on the 
right, and consequently a larger number of tumor emboli 
are deposited on that side of the organ. A similar distri- 
bution of tumor is seen in the spleen, where the infre- 
quency of tumor growth is so great as to give rise to the 
assumption that the spleen possesses a certain resistance 
to tumor growth. This hypothetical resistance has even 
been used to prove other points concerning a hypothetical 
immunity possessed by the human body. These two hypo- 
theses have been postulated to explain a phenomenon which 
is perfectly explicable on other grounds. In the first place, 
it has been shown that the spleen does not possess any re- 
sistance to tumor growth. In an animal, if the tumor is 
planted directly in the spleen it grows just as well in that 
organ as it does anywhere else; therefore, there is no local 
immunity. Secondly, metastases do occur in the spleen, and 
microscopic metastases are fairly frequent. They are 
usually missed because the spleen is not carefully studied 
in autopsies on persons dying of cancer, but it is estimated 

^Tyzzer: Jour. Med. Research, 1913, N. S. xxiii, 309. 

47 



that in at least 10 per cent, of persons dead from malignant 
disease the spleens contain microscopic metastases. Large 
metastases in this organ are, however, rather infrequent 
in carcinoma, though they are more often seen in sarcoma. 
The reason for the infrequency of carcinoma metastases in 
the spleen, when, as will be recalled, carcinoma of the 
stomach is the most frequent type of malignant disease, lies 
in the simple anatomical fact that the spleen possesses no 
afferent lymphatrcs; in other words, there is no direct 
channel from the stomach, to the spfeen by the most usual 
route through which tumor cells are carried; and, conse- 
quently, all the tumor cells must be transplanted by the 
blood-vessels. The splenic artery branches off rather 
sharply from the celiac axis and particles would not be 
driven into this with any great frequency, but that they 
do reach the spleen is unquestioned. Here, however, the 
same condition as in the lung again exists, for the spleen 
is an organ which pulsates with every beat of the heart, 
and, therefore, the tumor cells are kept oscillating in the 
splenic sinuses and do not find a quiet resting place where 
they can obtain a foothold and gain the necessary nutri- 
tional equipment and support from the connective tissue. 
In other words, the apparent infrequency of metastatic de- 
posits in the spleen is due solely to anatomical and mechani- 
cal conditions.^ 

Transfer of Tumor Cells Through the Lymphatics 

The mechanical conditions which tend to spread the 
tumor cells through the lymph-channels are different from 
those which apply in the case of extension through the 

iChalatow, Virchows Arch., 1914, ccxvii, 140 (bibl.); Kettle, Jour. 
Path, and Bacteriol., 1912-13, xvii, 40; v. Hansemann, Deutsch. med. 
Wchnschr., 1915, xli, 633; Geipel, Virchows Arch., 1912, ccx, 358; Deel- 
man, H. T., Het metastatisch carcinoom van longen en milt in verband 
met de verspreiding van het carcinoom door het lichaam, Amsterdam, 
1918. 

48 



blood-vessels. While the epithelium of the carcinomata 
penetrates early the lymph-spaces of the surrounding 
tissue, as a rule, there is in these channels no active cur- 
rent, as there is in the blood-vessels, so that the dominant 
factors are different from those in the cell transported by 
the hemic system. A certain amount of progressive 
growth takes place through these lymph-channels, forming 
a continuous chain of cells until the nearest regional lymph- 
node is reached. Here the cells are held for a shorter or 
longer period, and develop as a rule into a nodule of new- 
formed tumor which preserves to a very considerable ex- 
tent the morphology of the original. Such continuous pene- 
tration is most easily observed in the tumors involving the 
serous coats of the pleural cavity or the peritoneum, and 
it is not uncommon to see the lymph-channels near a tumor 
of the intestine extend along the mesentery as white 
strands distended with carcinoma cells. The submucous 
coat of the stomach, also, may show similar lymphatic chains 
which cover nearly the entire organ, though the primary 
tumor may be a small mass near the pylorus. A similar 
occurrence has not infrequently been noted in connection 
with carcinoma of the breast, especially of the type known 
as cancer en cuirasse, where the skin is rendered firm and 
leathery by the filling of the lymph-spaces by cells of the 
tumor. Handley^ in an important monograph, has insisted 
upon the importance of this form of metastasis; and it 
was thought by many of the older writers to be the only 
type of invasion of the surrounding tissues. Serial sections, 
however, show that continuous invasion is not very fre- 
quent, but that the lymphatics contain nodules placed along 
their course like beads loosely strung on a string, and 
examples may often be found in which there is no involve- 
ment of the channels between the tumor and its nearest 

^Handley: Cancer of the Breast, London, 1908. See, also, a short 
review by Handley: Arch. Radiol, and Elec, 1919, xxiv, 137. 

49 



nodes, though the latter may contain metastases. Handley 
explains this discontinuity by assuming that the cells near- 
est the tumor die after a time and only the peripheral ele- 
ments which have arrived at or near the node survive. 

The opinion most generally accepted is that cancer cells 
travel rather by small numbers or as individual cells along 
the lymph-channels, aided perhaps in their passage either 
by the ameboid motions of which they are capable, as dem- 
onstrated by Carmalt,^ or by the massage of the tissues 
given by every muscular movement which takes place in 
the body. Just how much stress can be laid upon ameboid 
motion as a factor is still unsettled. Lambert and Hanes^ 
are inclined to consider it is very important, but the general 
opinion is that it is less vital than other mechanical means, 
especially massage. The lymph-current must be so slug- 
gish, even in the smaller lymphatics, that but little carry- 
ing power can be attributed to the flow itself. In the 
larger drainage channels and in the thoracic ducts the cur- 
rent flow unquestionably plays a part. 

That massage by muscular contraction is a vital factor 
is easily demonstrated by the extensive spread of the tumor 
cells in the submucosa or the muscularis of the stomach 
when the primary growth may be still exceedingly small 
or even undiscoverable. The entire organ may be converted 
into a hard, thick, rigid, cylindrical viscus simply by the 
presence of innumerable cells distributed throughout the 
lymph-channels by the muscular contractions of the stom- 
ach wall. A similar distribution takes place in the intestine, 
though the usual type of intestinal carcinoma, an alveolar 
form with large cells, is mechanically much less adapted 
to such distribution. A much better demonstration is, un- 
fortunately for the patient, occasionally seen in those in- 
stances of carcinom.a of the breast in which osteopathic 

iCarmalt: Virchows Archiv, 1872, Iv, 481. 

^Lambert and Hanes: Jour. Am. Med. Assn., 1911, Ivi, 791; Virchows 
Archiv, 1912, ccix, 12*. 

50 



treatment or massage has been applied ''to dissipate the 
tumor" by rubbing or in those in which the possessor has 
used massage without instruction. In such instances the 
whole thorax may be covered by an enormous number of 
skin nodules, and extremely early involvement of the bone 
marrow and all of the organs of the body often occurs. 
Even the manipulation which is ordinarily carried out in 
the course of diagnosis may result in the distribution of 
the tumor cells, a matter which is too often forgotten. 
During the operation, also, any manipulation or pressure 
on the tumor should be avoided, for it is more than probable 
that many of the local recurrences which are observed 
after a perfectly executed operative removal of a mammary 
carcinoma are due entirely to such massage. It is only 
rarely that extensive metastatic nodules are seen in the 
skin in unoperated carcinoma of the breast except in the 
very latest stages, while after operation such nodules are 
unfortunately met with with unpleasant frequency. 

When the tumor-cells reach the lymph-nodes they are 
deposited first in the peripheral sinuses, and if the trans- 
port does not continue the whole of the metastatic deposit 
may be confined to such sinuses. Gradually, however, the 
•growth invades the central portion of the node and ultimate- 
ly all lymphoid tissue may be destroyed and only a mass of 
carcinoma with more or less connective tissue stroma re- 
sult. Not every enlarged lymph-node in a case of carcinoma 
is necessarily the site of a metastasis; apparently lymph 
stasis alone is responsible for a very considerable swelling 
of the nodes, which, if treated by x-ray or radium, will 
finally disappear ; and many of the highly optimistic reports 
of the results of the use of these agents are based upon 
such disappearances. If, hov/ever, carcinoma is present 
in the node, while the lymphoid tissue may vanish, the 
tumor will continue to grow. 

51 



Unquestionably also a certain number of cell emboli 
will die if left in the nodes, just as they die in the capillaries 
of the lung. It has also been frequently demonstrated that 
such small metastatic nodules may remain quiescent for a 
long period, provided that the primary tumor has been 
removed so that the patient survives for observation. In- 
stances are on record of recurrences in the nodes fifteen, 
twenty or even more years after the removal of carcinoma 
of the breast.^ According to modern operative technic the 
axillary nodes are usually thoroughly removed, so that such 
late recurrences have been most frequently noted in the 
nodes of the supraclavicular group. The presence of cancer 
cells in the nodes stimulates the latter to production of 
connective tissue which often is very extensive in scirrhous 
carcinoma. On the other hand, occasionally nodes are seen 
in which the production of stroma is a minimum, and areas 
of solid carcinoma lie in the sinuses and follicles without 
the occurrence of any change in the general morphology 
of the node. 

It is necessary to be exceedingly cautious in diagnosing 
early lymph-node metastases microscopically, for the prod- 
ucts of the metabolism of the tumor cells or of the bacteria 
which m.ay be present in ulcerating growths are capable of 
causing a chronic hyperplasia of the endothelium of the 
sinuses which simulates somewhat the appearance of car- 
cinoma. 

Usually the position and appearance of these large 
endothelial cells are sufficient to enable a differential diag- 
nosis to be made, but occasionally, instead of lying in the 
sinuses, they may occupy small areas either in the germinal 
centers or in the lymphoid tissue, and it is then exceed- 
ingly difficult to differentiate them from carcinoma. An- 
other complication frequently met with in the examination 

^Williams: Natural History of Cancer, New York, 1908, p. 454; and 
Deaver and McFarland: The Breast: Its Anomalies, Diseases, and Treat- 
ment, Philadelphia, 1917, p. 562. 

52 



of nodes of the pelvis and retroperitoneal region is the 
presence of tubular glands with high cylindrical epithelium 
or even ciliated epithelium, which are apparently remnants 
of glandular structures left during pre-natal existence; 
these may easily lead to a diagnosis of extensive metastatic 
carcinoma/ The writer has even seen collections of squam- 
ous cells in bronchial and retroperitoneal nodes in persons 
in whom no tumor could be demonstrated by autopsy. 

After the tumor has more or less completely involved 
the lymph-nodes of a given region, extension may take 
place either through lymph-channels to the next series of 
lymph-nodes, or, after invasion of the thoracic duct, 
through the general circulation; or, finally, the cells may 
penetrate the walls of the veins leading from the node and 
thus enter the blood stream. The supraclavicular nodes 
may be affected when the thoracic duct is invaded, but also 
without such invasion. It is important to remember in 
connection with metastases in the lymph-nodes that size 
of the node is by no means always correlated with the 
dimensions of the tumor giving rise to the aberrant par- 
ticles. There are a number of instances on record in which 
a very small tumor of the prostate or of other organs, 
though giving no clinical symptoms, has caused such ex- 
tensive metastatic enlargement of the nodes in distant por- 
tions of the body that the diagnosis of either Hodgkin's 
disease or lymphosarcoma was made, and only at autopsy 
was the primary tumor demonstrated.^ 

The size and the relationships of the tumor cells to 
each other and to the surrounding tissue are also a factor 
of importance in determining the extent of lymph-node 
metastasis in any given case. If the tumor is of an adeno- 
matous type, such as the carcinomata of the intestine, the 

^Meyer R.: Ztschr. f. Geburtsh, u. Gynak., 1903, xlix, 554; Sitzenfrey: 
ibid., 1906, Ivii, 419 (bibl.); Kernianuer and Lameris: Beitr. z. Geburtsh. 
u. Gynak., 1901, v, 87; and Scheib: Arch. f. Gynak., 1909, Ixxxvii, 1 (bibl.). 

^Lundsg-aard: Virchows Arch., 1913, ccxiii, 55. 

53 



cells are fairly firmly held together and are not easily sepa- 
rated from their anatomical relationships to each other and 
to the surrounding stroma. In this type, therefore, lymph- 
node metastases are late and fairly infrequent. On the 
other hand, if the tumor cells are loosely connected as in 
scirrhous carcinoma of the breast, where involvement of 
the regional lymph-spaces takes place very early, and espe- 
cially if the cells are small, very extensive lymph-node in- 
volvement may occur even when the primary tumor is of 
extremely moderate dimensions. It is not uncommon to 
see a tumor of the breast, not over 1 cm. in diameter, with 
widespread invasion of the axillary nodes, while the large- 
cell carcinomata of the breast may reach an enormous size 
and the axillary nodes still remain quite free of metastatic 
particles, even though the tumor has been in existence for 
several years. The same slow metastasizing power is seen 
in the gelatinous carcinomata of the breast, the lymph- 
nodes escaping for a long period, so that these tumors offer 
a better prognosis after operation than any other mammary 
type. 

Metastasis by Implantation 

Another form of extension of cancer is by implanta- 
tion. This is most frequently seen in the cavities, as the 
pleural and peritoneal. The tumors growing through the 
lining membrane of these cavities spread on the surface 
by direct growth in the form of flat masses. As a rule, it 
is not easy for the cells of a carcinoma to get a foothold 
unless there is accompanying inflammation, or damage of 
some sort to the endothelial coats, so that not infrequently 
a carcinoma of the stomach or gall-bladder may give rise 
to no peritoneal implantation, and there may be no in- 
volvement of the omentum ; whereas the ovaries may show 

54 



extensive bilateral carcinoma. It has been shown experi- 
mentally that if the surface of the peritoneal cavity is 
injured by the injection of sterile irritating substances such 
as diatomaceous earth, the implantation of carcinoma ex- 
perimentally introduced is much more apt to succeed than 
if the tumor cells are simply injected into the cavity.^ 

Other well known examples of implantation are seen 
in carcinoma following exploratory puncture or laparotomy 
wounds of the abdominal cavity in cases of a peritoneal car- 
cinoma, or implantation in the vagina following operative 
removal of a carcinoma of the cervix. 

While many instances have been described of contact 
implantation, for example, a carcinoma of the upper lip fol- 
lowing the appearance of one on the lower lip at the point 
of contact of the two surfaces, or of a squamous-cell epithe- 
homa arising in the vulva at the point exactly opposite an- 
other vulvar carcinoma, yet there are a number of reasons 
for thinking that such implantation must be of exceedingly 
great rarity, even though it is granted that the persons 
who have a carcinoma are extremely sensitive to implanta- 
tion of their own tumor. The reasons for disbelieving many 
of the reported cases of direct contact implantation are, 
first, that the surface cells of the carcinoma are most of 
them desquamating and dead, and second, that the surface 
on which they are implanted is usually healthy, and there- 
fore resistant to the implantation of cells, just as the skin 
of a surgeon's hand is resistant to the implantation of the 
carcinoma cells which touch it during the course of an 
operation. Nevertheless, there are probably a certain num- 
ber of contact implantations taking place after a sufficient 
period has elapsed for the ulcerated surface of the tumor 
to irritate or inflame the opposing mucous membrane and 
give rise in this fashion to a suitable bed for the growth 
of such cancer cells as may be derived from the primary 

iJones and Rous: Jour. Exper. Med., 1914, xx, 404. 

55 



tumor. Most of the cases, however, can be interpreted by 
metastasis rather than by contact.^ It is also possible that 
the irritation of the carcinoma may so alter the mucous 
membrane with which it is in contact that an entirely new 
growth may originate from this site. 



Organs Involved by Metastasis 

Metastases in other organs than the lymph-nodes are 
common. The liver is the most frequent structure to be 
attacked. In this area enormous tumors often grow, in 
some instances greatly exceeding in bulk the original size 
of the organ. Its double circulation brings it metastases 
not only from the general circulation through the hepatic 
artery, but also, by means of the portal vein, from all the 
organs of the abdominal cavity. Either the tumors grow 
as solitary masses compressing and causing absorption of 
the liver tissue as they develop, or the whole liver may be 
diffusely infiltrated and the sinusoids filled with tumor 
cells. A third means by which metastases may reach the 
liver is by retrograde embolism from the sub-hepatic nodes 
through the lymph-channels in the hilus, thus draining the 
tumor cells from the stomach, pancreas, and duodenum. 
In the peritoneal cavity metastases are also extremely fre- 
quent, arising almost entirely from organs which lie in that 
area. The omentum is often attacked, and the cells may lie 
throughout that tissue, forming small nodules, so that the 
lesion resembles very closely miliary tuberculosis. More 
extensive involvement is not infrequent, in which case the 
omentum forms a thick cake largely composed of cancer 
cells. Metastases are also very frequent in the lung, reach- 
ing these organs either by the blood-stream or through the 

^Borrmann: Deutsch. Ztschr. f. Chir., 1905, Ixxvi, 404; Milner: Arch, 
f. Chirurgie, 1904, Ixxiv, 669 and 1009. 

56 



lymph-nodes from the hilus. The tumor may spread 
through the lymph-channels of the visceral pleura, inject- 
ing them to form white, irregular, interlacing channels. 
The tumors may form discrete masses compressing the 
lung tissue, or they may invade the alveoli, filling them 
with cancer cells, or, in some instances, they may remain 
largely peribronchial in distribution, transforming these 
tubes into rigid pipes. The bone marrow, also, is frequently 
invaded, much more often than is generally appreciated. 
The secondary tumors may remain quiescent for a time, 
even for some years, and give no clinical evidence of their 
presence, or they may cause softening and absorption of 
the bone, which is easily demonstrable by Roentgen rays. 
Spontaneous fractures occur in consequence of these 
changes. In rare instances, the marrow invasion incites 
severe anemia and even a blood picture superficially re- 
sembling myelogenous leukemia. Metastases in other 
organs are less frequent. The muscle tissues, as has been 
stated, are usually spared; and the stomach and intestine 
are rarely involved secondarily. Splenic involvement has 
been previously discussed. Metastases have been described 
in the tonsils, in the teeth, and in the walls of the larger 
blood-vessels, especially the aorta; they are fairly frequent 
in the central nervous system and spinal cord; they are 
seen occasionally in the nerve trunks; they may involve 
the eye ; and, finally, they may occur in the mamma, uterus, 
and especially the ovaries, the last being involved in about 
7 per cent, of the carcinomata of the mamma. Skin meta- 
stases at a distance from internal carcinomata are infre- 
quent, about one instance being noted in five thousand pa- 
tients dying of carcinoma.^ Dermal metastases of sarcoma, 
especially the melanotic types, are common. They occur 

^Suzuki: Multiple skin metastases from cancer of internal organs, 
Jour. Cancer Research, 1918, iii, 357. 

57 



chiefly following mammary tumors or those of the diges- 
tive tract. Mammary tumors, of course, furnish the most 
frequent skin metastases, but usually in the neighborhood 
of the tumor itself, and by direct extension. One tumor 
may even metastasize in another, and the writer has seen 
a metastasis of a carcinoma in the placenta.^ 

DEGENERATIVE CHANGES IN TUMOR TISSUE 

Degenerative changes of varying types occur in the 
tissues of benign and malignant tumors, but by no means 
differ from alterations which occur in normal structures 
v/hen the blood supply is diminished or ulceration and 
cachexia have occurred. Tumors, are, however, more liable 
to sudden hemorrhages with subsequent degeneration, first, 
because of the extraordinary demands made upon the 
usually insufficient blood supply by the rapidly growing 
cells, and, second, because of the very imperfect character 
of the capillary circulation, which leads to thrombosis either 
by stasis or by pressure or by invasion of the wall of 
vessels by the tumor cells. Tumors, if pedunculated, may 
have their circulation restricted or wholly checked by tor- 
sion of the pedicle. The results of all these changes are: 
1, hemorrhage, and, 2, degeneration of various types lead- 
ing ultimately to necrosis or gangrene. The earlier stages 
may show only fatty degeneration of the cells which may 
progress to ultimate calcification or even bone formation. 

EFFECT OF TUMORS ON THE ORGANISM AS A 

WHOLE 

The belief is still widely held that cancer cells con- 
tain toxic substances which act in a deleterious fashion 
upon the organism as a whole. This opinion, however, has 

^See, for another case of carcinosis of the placenta from a gastric 
tumor, Senge: Ziegler's Beitr., 1912, liii, 532. 

58 



been based largely upon clinical observation of patients with 
malignant tumors, a notoriously difficult field, and lacks 
final confirmation. It is true that Underhill and Woodruffs 
thought they had shown that human carcinoma exerted a 
depressing effect on Paramecium aurelia. They used ex- 
tracts made by mincing tumor tissue, adding water, and 
heating the mixture to the boiling point. Their controls 
were unsatisfactory, however, and the question of a specific 
cancer toxin must be regarded as unsettled. 

Calkins^ repeated this work, using Didinium nasutum, 
and believed he obtained evidence that there was both a 
stimulating and a lethal factor present in fresh minced 
adenocarcinoma of the mouse; but he found that rapidly 
growing normal epithelium also stimulated Didinium, and 
if he had used comparable quantities would no doubt have 
found the lethal factor also. 

Experiments on human beings have been carried out on 
a fairly large scale by those who believe that cancer can 
be influenced by a ^'vaccine" composed of ground-up tumor 
tissue. These experiments showed two things: 1, that no 
evidence of a poison or toxic material could be found after 
such injections, and, 2, that a human being could be inocu- 
lated very readily with his own tumor, for in several un- 
fortunate instances whole cells were evidently left in the 
minced tissue with the result that numerous metastases 
were produced. Again, the injection of autologous cancer 
tissue in animals — and this is the only true test, for a pri- 
mary tumor is part of the host's own tissues — does not 
produce the slightest effect unless the amount is over- 
whelming.^ 

lUnderhill, F. P. and Woodruff, L. K: Jour. Biol. Chem., 1913, xv, 401. 

^Calkins, G. N.: Jour. Cancer Research, 1916, i, 205. 

^For further details concerning- these points, consult v. Fiirth- 
Probleme der physiologischen und patholog^ischen Chemie, Leipzig-, 1912- 
Blumenthal: Asher-Spiro, Ergebn. d. Physiol., 1910, x, 367, 409; and 
Neuberg-: Ztschr. f. Krebsforsch., 1911, x, 55. 

59 



Cachexia 

If a cancer cell does not contain or excrete a toxic 
material, it is obvious that what has been described clini- 
cally as cachexia and considered to be the result of the ac- 
tion of this poisonous substance on the human organism, 
lacks scientific verification. In fact, the opinion is rapidly- 
gaining ground that cancer of itself causes no disturbance 
in the body, and that the condition termed cachexia is due 
to mechanical interference with the function of important 
organs by pressure and destruction of the cellular struc- 
tures, interference with the movements of the gastrointes- 
tinal tract, hemorrhages from ulcerated tumors, and absorp- 
tion of bacterial toxins produced on the ulcerated surface 
and in the substance of the neoplasm. Other factors are 
unquestionably pain, v/hich causes sleeplessness, and lack 
of appetite, plus the psychic depression which affects those 
cancer patients who realize the gravity of their condition 
and are not under the stim.ulus of treatment of any sort.^ 

In confirmation of this opinion is the w^ell known fact 
that animals may carry large tumors, either primary or 
transplanted, v/ithout any evidence of cachexia,- and that 
human patients likewise miay harbor malignant tumors 
weighing several kilogram.s without evincing the slightest 
evidence of cachexia. This has been noted especially of 
late in connection with the widespread use of various type 
of radiation. Not infrequently patients whose lungs con- 
tain large numbers of metastases following an operation 
for carcinoma of the breast have been noted to gain in 
weight and to retain their normal hemoglobin, good color, 
nitrogenous balance, weight, and physical activity, though 
within a few weeks of death. By a recent study ^ on pa- 
tients bearing fairly advanced tumors, it has been shown 

^v. Hansemann: Ztschr. f. Krebsforsch., 1906, iv, 565. 
^Woglom: Study of Experimental Cancer, New York, 1913. 
^Theis and Stone: Jour. Cancer Research, 1919, iv, 349. 

60 



that changes in the composition of the blood are by no 
means invariably present, and when found are no greater 
than in many other wasting diseases. 

These facts being accepted, and there is no reason to 
doubt them, it is obvious that the various methods for the 
diagnosis of cancer based upon chemical and physical 
studies of the blood and excretions are so variable that they 
are of no value in determining the presence of a cancer un- 
less the neoplasm has reached such a size as to render the 
diagnosis possible by physical signs. When the patient 
begins to suffer from starvation, emaciation, anemia, and 
other terminal effects of the presence of a tumor in the 
organism, chianges naturally occur in the secretions and 
excretions of the body.^ 

Interesting changes in sugar tolerance have been ob- 
served in persons suffering from cancer, but sim.ilar altera- 
tions have been noted also in those with tuberculosis or 
diabetes and in pregnant women.^ 

Malignancy 

The question of the clinical malignancy of a tumor is 
decided largely by mechanical conditions, and not by the 
chemistry of the tumor cells. If the latter invade the 
vessels and neighboring lymph-nodes, they destroy import- 
ant functional organs of the body and interfere with health. 
Even the malignant tumors, however, may not exert any 
visible deleterious influences on the organism, as has just 
been pointed out, unless they seriously interfere with the 
general nutrition; and on the other hand, benign tumors 
may by pressure on organs or nerve trunks, by traction, or 

iKahn, M.: Diagnosis of cancer, Jour. Lab. and Clin. Med., 1916-17, 
ii, 103 (bibl.). 

^Rohdenburg-, Bernhard, and Krehbiel: Jour. Am. Med. Assn., 1919, 
Ixxii, 1528; Am. Jour. Med. Sc, 1920, clix, 577. 

61 



by causing intussusception, as is not infrequently seen in 
the lipomata of the intestine, cause serious disturbance of 
health, under which circumstances they may be described 
as malignant by position, if not by biological qualities. The 
assumption that the cellular infiltration so often seen about 
malignant tumors is a response to some cancer toxin is 
disproved by the fact that such infiltration is most abun- 
dant in the neighborhood of slow growing or receding 
tumors, and that it occurs also about grafts of normal 
tissue. 

It is quite probable that the metabolic products of a 
large malignant tumor, even though they are the same as 
a normal cell of the same type, may occasionally have some 
slightly injurious effect upon the organism, just as exces- 
sive secretion of the thyroid gland is deleterious; but that 
such intoxication can in any degree account for the rapid 
wasting seen in advanced cachexia, especially in that of 
gastric cancer, is in a high degree improbable. 

TUMORS IN ANIMALS 

Some twenty-five years ago, it was demonstrated by 
Jensen, Loeb, and others that it was possible to transfer 
spontaneous tumors arising in white mice and rats to other 
healthy individuals of the same species, though never to 
animals of other species. With the growing interest in 
the subject, it was shortly afterward found that tumors 
comparable to those occurring in man occurred also in many 
of the lower animals, and successful transplantations of 
such tumors have been carried on in guinea-pigs, rabbits, 
dogs, and fowls. Some of the tumors in mice and rats have 
been propagated in this fashion for nearly twenty years, 
without any evidence of important alterations, either in 
their morphology or in their biological qualities. Another 

62 



factor in the experimental study of cancer has been the 
recent observation that certain strains of white mice are 
prone to develop large numbers of primary tumors, if kept 
to the cancer age, some strains yielding as high as 40 to 50 
per cent, of tumors under these conditions. Thus, a power- 
ful method was available for the experimental study of the 
biology of tumor cells and the conditions of their appear- 
ance and growth, and an enormous amount of extremely 
valuable material has been collected. On the other hand, 
owing to the disregard of the simplest rules of statistics 
and common sense, many erroneous conclusions have been 
drawn by those working with animals. It has not been suf- 
ficiently appreciated, for example, that transplanted tumors 
are by no means strictly comparable to primary tumors 
in man or even to primary tumors in animals. Such a trans- 
planted tumor is merely a culture of tumor cells in a living 
host and is subject to many influences which modify the 
percentage of takes on inoculation and its growth rate, in- 
duce spontaneous disappearance, and have other effects not 
observable in primary tumors which are not merely grafts 
growing in a culture medium, but portions of the tissues 
of the hosts. Even after the grafted tumors have become 
thoroughly adapted to a given strain of animals, they show 
many unexplainable fluctuations in their growth. Such 
adaptation must be obtained before propagation can be suc- 
cessful, since usually the first transplants from a primary 
tumor yield only a small percentage of takes and a large 
number of transplants are necessary to get the tumor into 
a condition where it grows in a considerable percentage 
of inoculations. In many instances the establishment of 
such adaptability is impossible for reasons not as yet un- 
derstood. 

Among the interesting results of the study of trans- 
planted tumors are observations on the question of dosage 
of tumor implanted — small quantities giving better results 

63 



than large; the fact that the site of inoculation must be 
one which affords ample vascular supply; the fact that 
young animals offer a better soil for growth than do old 
animals, although it is in old animals that the tumors 
originate; the discovery of strains resistant to implanta- 
tion; the production of immunity to inoculation by the in- 
jection of homologous cells; the histological studies of the 
conditions for successful grafting; variations occurring in 
the tumor parenchyma and stroma during transplantation ; 
fluctuations in growth energy; and many other observa- 
tions vital to the cancer problem. The possession of strains 
of transplanted tumors of known biological qualities has 
permitted the demonstration of the importance of massage 
as a means for the rapid distribution of tumor particles 
throughout the body, and the relative harmlessness in the 
causation of metastasis of incision into tumors for diag- 
nostic purposes as compared to massage. It has permitted, 
also, the accurate determination of the lethal dose of radium 
and x-ray on the cancer cell. The study of these trans- 
plants has shown, also, that dietary restrictions do not in- 
fluence tumors unless the animal is starved so completely 
as to endanger life. It has permitted the demonstration 
that no vegetable, mineral, or biological substance admin- 
istered internally has any appreciable effect in causing dis- 
appearance of the tumor. The study of primary tumors 
in animals has confirmed several of these observations and 
has also led to the conclusion that heredity plays a part 
in the liability to tumor occurrence in animals, if not in 
man. 

Rous has shown on a chicken sarcoma that it is trans- 
plantable by a virus, but all attempts to transfer in this 
way tumors of other types have failed. Interesting studies 
have also been made of the biology of tumors growing in 

64 



the membranes of the chick embryo and in the plasma of 
various animals in the test-tube.^ 



SPECIAL TYPES OF TUMORS 

FIBROMA 

The name fibroma designates a type of tumor consist- 
ing chiefly of connective tissue cells and intercellular sub- 
stance. Such tumors contain in addition blood-vessels, in- 
cluded nerve filaments, and occasionally small areas of fat 
tissue. The two chief types of fibroma are fibroma durum 
or hard fibroma and fibroma molle or soft fibroma. 

(A) . The bulk of the tissue composing a hard fibroma 
has a structure resembling the dense connective tissue of 
the fasciae and ligaments of the body, being composed 
largely of bundles of collagen fibers with relatively few 
spindle-shaped cells. The cut surface is white or pale pink. 
The blood-vessels are few. The consistency is very firm, 
and even macroscopically one can often make out the in- 
terlacing broad bundles of connective-tissue fibers. The 
tumor is usually encapsulated and sharply defined from the 
surrounding tissue, except in the keloid type. It may exist 
as a symmetrical, circumscribed mass in the subcutaneous 
tissues or organs, but may also assume a polypoid form. 

Growth is, as a rule, slow, and the tumors are usually 
benign in their clinical course, though the keloid form fre- 
quently recurs and occasionally a very vascular fibrous 
polyp may cause erosion of the surrounding tissues by its 
growth. 

Degenerative changes may take place in the interior 

^For further details concerning the experimental side of cancer 
research, see Woglom: The Experimental Study of Cancer, New York, 
1913, which brings the bibliography of the subject up to 1913. The later 
experimental work may be found in the files of the Journal of Experi- 
mental Medicine, the Journal of Medical Research, the Journal of 
Cancer Research, and the Zeitschrift fiir Krebsforschung-. 

65 



of hard fibromata, and areas may become somewhat soft- 
ened by myxomatous degeneration of the fibrous tissue. 
Calcification may occur if the tumor has existed for a con- 
siderable time/ and occasionally true bone may be formed. 

These tumors may arise in any area where fibrous 
connective tissue exists. They are frequently found in 
the subcutaneous connective tissue, on the fascia of the 
muscles, periosteum, and sheaths of nerves, and in the 
ovary. More rarely they are found in the kidney, mamma, 
and uterus, though in the two organs last mentioned the 
tissue is apt to contain some of the epithelial or muscular 
structures derived from pre-existing tissues. Fat tissue is 
abundant in some of the fibromata. 

Microscopically, hard fibromata show chiefly interlac- 
ing bundles of connective tissue which may be united into 
homogeneous, evenly staining bands. This structure is per- 
haps noted more frequently in the clinical types known as 
desmoid^ and keloid,^ the first occurring largely in the an- 
terior abdominal wall, the other forming in the scars of 
cutaneous injuries. These may be simple accidental 
wounds, puncture wounds of the ear for ear rings, vaccina- 
tion or hypodermic scars, or burns produced by acids, caus- 
tics, or heat. They are especially frequent in negroes. The 
cells have small spindle-shaped or oval nuclei placed parallel 
to the general direction of the connective tissue fibers and 
often show no protoplasm around the nucleus. Larger 
nuclei with a considerable cell body may be found in the 
walls of the blood-vessels of the lymph-spaces, but if such 
large nuclei are frequent elsewhere, and if they are hyper- 
chromatic or multiple, and especially if a few show mitoses, 
a sarcoma should be suspected. Occasionally a plasma or 
mast cell may be encountered, and a small amount of elastic 

^Gergo: Virchows Arch. f. path. Anat., 1913, ccxiii, 317. 
2Pfeiffer: Beitr. z. klin. Chir., 1904, xliv, 334. 
s^ilms: Beitr. z. klin. Chir., 1899, xxiii, 149. 

66 



tissue can be demonstrated by suitable stains. Blood-vessels 
are not usually extensively developed; occasionally, how- 
ever, large dilated trunks run through the tumor. 

(B). The soft fibroma corresponds in its substance to 
areolar connective tissue. The collagen fibers are fewer; 
the meshes of the tissue are quite loose, and are often 
filled with mucoid material; the connective-tissue cells are 
more abundant; and such a tumor is usually well supplied 
with vessels, especially the polyps of the nasopharynx. 
Wandering cells, and eosinophilic, basophilic, and plasma 
cells are also abundantly present in the soft fibromata, 
especially along the course of the blood-vessels. 

It is not always easy to determine the boundaries be- 
tween the soft and hard types, and the exact designation 
is often a matter of personal opinion. Not infrequently 
also the tumor may be hard in one portion and soft in an- 
other. 

Soft fibromata are most frequently met within the 
polypoid growths of the nasal mucous membrane and in the 
skin. In the last mentioned region, they may be of a soft 
edematous type, the so-called fibroma molluscum, which 
are frequently multiple, or they may form soft ovoid nodules 
in the corium. 

The origin of multiple fibromata (neurofibromata, 
fibroma molluscum) is in all probability to be referred to 
a congenital abnormality.^ They are frequently distributed 
along the nerve bundles, springing from the endoneurium, 
and are often sym_metrically arranged in relation to the 
lateral halves of the body. Originally formed in the sub- 
cutaneous tissue, these tumors may stretch the skin and 
become pedunculated. In some rare instances, the fibro- 
matous growth involves the nerve trunks of a large portion 

^Harbitz: Arch. Int. Med., 1909, iii, 32 (multiple neurofibromatosis); 

Helmholtz and Gushing-: Am. Jour. Med. Sci., 1906, cxxxii, 355 (scalp 

tumors only); and Anderson: Jour. Am. Med. Assn., 1920, Ixxiv, 1018 
(generalized neurofibromatosis). 

67 



1 



of the body, forming the so-called plexiform neurofibroma. 
The nerve tissue, however, plays an entirely passive role 
in the process, there being no new growth either of nerve 
fibers or of ganglion cells, and in the latter stages even the 
nerve fibers may be so diluted by the great production of 
fibrous tissue that they may be impossible of demonstra- 
tion. Sarcomata develop in a considerable proportion of 
the neurofibromata.^ 

Some of the rare thickenings of the skin and subcuta- 
neous tissues seen in congenital elephantiasis may be con- 
sidered as a type of diffuse fibromata. The changes con- 
sist of a thickening of the cutis with excessive formation 
of fibrous connective tissue. Dilated lymph-vessels and 
blood-vessels are common in the tissues of the tumors, so 
that one may speak of a lymphangiectatic or of a heman- 
giectatic elephantiasis. The growths are probably closely 
related to the neurofibromata. 

The clinical course of the fibromata is, in a vast ma- 
jority of instances, benign, though they may interfere with 
bodily function by pressure or traction. Occasional in- 
stances have been observed in which a recurrence after in- 
complete removal is undoubted. As an example may be 
cited a patient^ who had a small fibroma of the abdominal 
wall removed, and four years after developed a very large 
tumor at the site of the original cicatrix. The recurrence 
penetrated between the muscles, but was generally encap- 
sulated except for a few branching projections which pene- 
trated the muscular planes. Microscopical examination 
shov/ed that it retained the characters of a fibroma. 

Ribbert^ has also reported a successful autotransplan- 
tation of a fibroma, though the attempt to transfer the 
growth from the original host to another animal failed. 

iGarr6: Beitr. z. klin. Chir., 1892, ix, 465. 

^Senlecq and Chenot: Fibrome recidive de la parol abdominale, Bull, 
et m6m. Soc. anat. de Paris, 1911, 6 s6r., xlii, 265. 
3Ribbert: Centralbl. f. allg. Path., 1910, xxi, 62'5. 

68 



This is not exactly comparable to a recurrence, but shows 
a considerable power of independent growth residing in the 
tumor tissue. The writer has seen also a transplantable rat 
tumor (Crocker Fund Rat No. 39) resulting from the im- 
plantation of a fibroadenoma of the breast, which has sur- 
vived eleven generations ; but in all such examples the pos- 
sibility of a fibrosarcoma must be considered. 

The diagnosis of the subcutaneous, fascial, or perios- 
teal fibromata is usually a matter of clinical examination 
only. The subcutaneous tumors require careful study to 
eliminate fibrosarcoma. Small, hard, painful microscopic 
nodules in the skin (tubercula dolorosa) often include a 
small nerve filament.^ The vascular polyps of the naso- 
pharynx are, in a large majority of instances, benign, but 
occasionally they are so cellular and contain so many blood- 
sinuses as to give rise to the suspicion of sarcoma. Keloids, 
even though recurrent, are in general clinically so well char- 
acterized that the microscopic examination is only confirm- 
atory. 

In general, a hard, lobulated, freely movable, and en- 
capsulated tumor is a fibroma, but many of the subcutane- 
ous sarcomata have exactly the same physical qualities, 
and surgeons have yet to learn that the slow-growing sar- 
comata may be well encapsulated and freely m.ovable. 

MYXOMA 

Myxomata are tumors composed of mucous tissue. The 
characteristic tissue in the myxomata is a cell-containing 
mucous structure resembling that in Wharton's jelly of the 
umbilical cord. While true myxomatous tissue is an essen- 
tially embryonic structure and is not found normally in the 
adult human body, it may develop from fibrous connective 

iWood, Wm.: Edinburgh Med. and Surg-. Jour., 1812, viii, 283, 429; 
Virchow: Die krankhaften Geschwiilsten, Berlin, 1863, iii, 236. 

69 



tissue, fat, and cartilage under certain pathological condi- 
tions. Ribbert, however, believes all myxomata are derived 
from aberrant tissue remnants.^ This metaplastic change 
must be carefully differentiated from the edema with gela- 
tinous softening which so frequently appears in the same 
tissues and closely simulates mucous tissue morphologically. 
In this latter condition the interstitial substance softens 
and the cell fibers are pressed apart, the space being filled 
with a more or less fluid mass which takes the hematoxylin 
stain. Such changes occur frequently in the fibroadenomata 
of the breast and in nasopharyngeal polyps, but tissue so 
formed is not true myxomatous tissue. 

The tumors are met with in all regions of the body, 
most frequently as subcutaneous or submucous masses on 
the extremities. They may form new growths, often multi- 
ple, along the peripheral nerve trunks, the nerve tissue, as 
in the neurofibromata, playing a passive part. Occasion- 
ally, myxomata have been found at the umbilicus and in 
the mesentery or retroperitoneally ; such growths often 
contain much fat tissue. A site of pathological interest is 
the endocardium.2 Myxomatous tissue is also frequently 
present in the complex tumors of the salivary glands, some- 
times forming the greater portion of the growth. In gen- 
eral, myxomata of the pure type are infrequent. 

The gross appearance of these tumors is very charac- 
teristic. They are usually fairly well outlined, round, no- 
dular, or lobulated masses, and are frequently, though not 
always, encapsulated. The softer varieties are so elastic 
that they simulate a thick walled cyst. Diffusion through 
the surrounding tissue points strongly to a sarcomatous ele- 
ment in the growth, though it may occur after local recur- 
rences of the benign types. The tissue is very transparent 

iRibbert: Frankfort, Ztschr. f. Path., 1910, iv, 30; also Geschwulst- 
lehre, 2nd ed., Bonn, 1914. 

'Hagedorn: Centralbl. f. allg. Path. u. path. Anat., 1908, xix, 825. 

70 



and when the tumor is squeezed the gelatinous substance 
flows out in irregular clear masses which are more or less 
sticky and form long threads when the surface is scraped. 
Capillaries and strands of connective tissue can usually be 
seen with the naked eye, and large hemorrhagic areas or 
blood cysts are not infrequent. The color of the cut sur- 
face is greyish or yellowish, the latter shade being depen- 
dent upon the fatty degeneration of the cells and the 
amount of fat tissue mixed with the myxomatous tissue. 
If the blood-vessels are very abundant the tumor assumes 
a pinkish shade. 

Microscopical examination of the myxomata shows the 
tumors to be largely composed of a jelly-like substance con- 
taining fine fibrils and cells characterized by their irregular 
shape and the long prolongations which run in all directions 
through the basement substance. These prolongations from 
the cells are very narrow, curved or bent, and frequently 
interlace. The cells often show fatty degeneration. They 
usually contain a single nucleus, but occasionally multinu- 
clear cells have been observed which are usually without 
prolongations. Blood-vessels are apt to be fairly abundant. 
If many large or giant cells are found the tumor is in all 
probability not a true myxoma, but a myxosarcoma. The 
difference between the two forms is often difficult to deter- 
mine, and it is necessary to examine sections from all por- 
tions of the growth, for some parts may show only pure 
myxomatous tissue, others pure fibrous tissue, and still 
others tissue of an evidently sarcomatous nature. 

The myxomata are very rarely wholly composed of 
mucous tissue. In the majority of the cases the myxomat- 
ous portions are mingled intimately with connective tissue, 
fat,^ and cartilage.^ Whether this is due to a metaplasia 

^Robertson: Lipoma myxomatodes, Jour. Med. Research, 1916-17, N. 
S., XXX, 131 (bibl.). 

^Seitz: Deutsch. Ztschr. f. Chir., 1905, Ixxviii, 60. 

71 



of tissues into myxomatous tissue, or whether the develop- 
mental defect which is responsible for the mucous tissue is 
likewise responsible for the cartilage is as yet unsettled. 
The latter theory perhaps better explains the facts, espe- 
cially if we consider the close relationship betwen the myxo- 
matous areas so frequently found in the congenital com- 
plex tumors of the region of the salivary glands. 

Pure myxomata are usually benign growths. The com- 
plex types take their clinical characteristics from the adven- 
titious cell types. The rare recurrences of pure myxomata 
are generally similar to the primary growth, and the diag- 
nosis is usually made easily; but they may be much more 
cellular and it is wise to be extremely cautious about the 
benign nature of an apparently pure myxoma. Those which 
are found in the subcutaneous tissue and can be thoroughly 
removed do not often recur, but after partial removal re- 
currence not infrequently takes place. One case in the 
writer's experience recurred twice, but after a third opera- 
tion no further return of the tumor was observed. Another 
returned twice, becoming more cellular each time, until 
finally a morphological diagnosis of myxosarcoma was war- 
ranted, and demonstrated by the fatal issue. Only the last 
recurrence infiltrated the tissues to any extent. In all cases 
where recurrences are noted, the microscopical diagnosis 
of myxoma should be questioned, for the tumor is then 
probably of a sarcomatous nature, as some portion of the 
growth will show if sufficient slides are examined. 

Usually even the gross aspects of these tumors are so 
characteristic that a diagnosis can be made at a glance, the 
only important differentiation being that required between 
the relatively benign myxomata and the malignant myxo- 
sarcomata. Both types are often encapsulated. The dif- 
ferential diagnosis may be quite difficult or even impossible 
from the microscopical aspect of the tumor, and then must 
be made from the clinical history. Usually, however, the 

72 



myxosarcomata are so much more cellular than the myxo- 
mata, the cells are so much larger and more irregular in 
type, and are in such close relation to the vessels, that a 
separation is possible. The very cellular myxomata should 
aways be considered clinically as myxosarcomata, except 
in the case of the complex tumors of the salivary glands, 
where the growth may contain a very considerable number 
of cells without always possessing the qualities of malig- 
nancy. 

LIPOMA 

Lipomata are tumors formed of fat tissue. The fat 
cells are usually arranged in small lobules, each lobule pro- 
vided with a vascular supply. The various lobules are 
sheathed by connective tissue which is sometimes very 
abundant, or sometimes very scanty in amount. The tumor 
is usually separated from the surrounding tissues by a well 
developed fibrous capsule, but cases are seen in which 
tumor-like masses of fatty tissue spread diffusely through 
the subcutaneous tissue of the body. The tumors may be 
spherical or oval or irregular in shape. Often they are 
strikingly lobulated. 

The cross section of a lipoma is a bright yellow color 
from the fat which the cells contain, and if examined im- 
mediately on removal from the body, the fluid fat may run 
from the cut surface. The color is, however, often a little 
lighter than the normal body fat. 

The cells which compose the tumor are usually mature 
fat cells of large size with but a remnant of cell body en- 
closing a fat globule, but occasionally in rapidly growing 
lipomata or after trauma affecting fatty tissue, areas are 
found in which developing fat cells are seen composed of 

73 



a granular cytoplasm containing only a few small, fat par- 
ticles or none at all. Very often such cells are multinu- 
cleated.^ 

These tumors may show such power of penetration of 
the normal surrounding tissues as to hint that they may 
have certain elements of malignacy.^ In one instance 
large quantities of embryonal fat tissue were found dis- 
tributed in various portions of the body, chiefly in the fas- 
cial planes, connective tissue, and loose tissues of the 
thorax and abdomen. The tumor material was of a cherry 
red color and was arranged in a trellis-like distribution 
with oval and rounded tumors measuring 3 to 5 mm. His- 
tologically, these tumors showed the presence of richly 
cellular islands lying in a reticulum of loose connective 
tissue. The islands were composed of a network of capil- 
laries between which lay the groups of polyhedral cells con- 
taining small fat granules. The nuclei were centrally 
placed in the granular cytoplasm. 

Lipomata occur almost anywhere in the body. Most 
often they are subcutaneous. They are also found in the 
joints, meninges and brain, lungs, liver, kidney,^ mamma, 
gastrointestinal tract, round ligament, and vas deferens, 
and occasionally in other places.* 

Lipomata are occasionally multiple and symmetrically 
arranged as regards the two halves of the body. Occurring 
in this fashion they are often closely connected with the 
nerve trunks, and are probably due to some congenital ab- 
normality of the tissue, and are sometimes associated with 
trophic, sensory, or motor disturbances, and even endocrine 

^Merkel: (tumor of breast) Zeiglers Beitr., 1906, xxxix, 152; Rasov: 
(tumor of back) Frankfort. Ztschr. f. Path., 1913, xiv, 359. 

^Symmers and Fraser: The significance of embryonal fat cells in 
certain pathological conditions. Arch. Int. Med., 1917, xix, 699. 

sReenan and Archibald: Jour. Med. Research, 1907, N. S. xi, 121. 

*The bibl. up to 1906 will be found in Schridde, Lubarsch-Ostertag, 
Ergebn. d. allg. Path., 1906, x, 674. 

74 



conditions, such as hyperpituitarism. '^Lipomatosis dolo- 
rosa" is probably of this type.^ In another congenital type 
the fat fills clefts in the normal body structures, as, for 
example, in spina bifida and such "teratoid lipomata" may 
contain, in addition to the fat, muscle, bone, cartilage and 
even brain substance. 

An excessive development of blood-vessels may give 
rise to a type of tumor which is designated cavernous 
lipoma or angiolipoma.^ Areas of fatty tissue are fre- 
quently found in tumors, especially those of congenital 
origin, such as the retroperitoneal myxomata and the tera- 
tomata of the pelvic region. Secondary changes such as 
calcification are not uncommon, even the formation of bone 
has been observed in a very few cases. 

Pure lipomata are benign growths. They may be ex- 
tremely painful or may interfere with bodily functions by 
mechanical means,^ or in pedunculated growths, by necrosis 
or infection secondary to torsion of the pedicle, but true 
recurrences indicate the presence of sarcoma in the sup- 
posed pure lipoma. 

XANTHOMA 

Although ordinarily included in the tumor group for 
convenience, many of the xanthomata are probably not 
tumors in the strict sense, but are instead an inflammatory 
or degenerative process affecting connective tissue and 
muscle cells, thus giving rise to tumor-like masses or flat 
plaques in various parts of the body. Three types of xan- 
thoma are commonly recognized : 

1. Xanthoma palpebrarum (xanthelasma), by far the 

iLyon: Arch. Int. Med., 1910, vi, 2"8. 

^Kiepke, H., Virchows Arch., 1919, ccxxvi, 64 (malignant angioli- 
poma). 

sKothny, C. K., Wien. klin. Wchnsch., 1920, xxxiii, 65. 

75 



most frequent type, forming flat, slightly elevated yellowish 
plaques which usually occur symmetrically on or about the 
eyelid. The tumor cells are generally held to be degenerated 
muscle fibers ;^ but others believe them to be embryonal fat 
cells or fatty, degenerated fibroblasts or endothelium. 

2. Multiple xanthomata, which form nodules especial- 
ly on portions of the body exposed to trauma such as the 
extensor surfaces of the elbow, and knee joints, but also 
internally,^ and are composed of cells altered by fatty de- 
generation derived from fibroblasts or endothelium. 

3. Xanthoma diabeticorum, in which yellow nodules 
appear in various parts of the body, usually subcutaneously, 
but occasionally in the internal organs. 

The xanthomata about the eyes are yellowish or 
brownish flat tumors, which are quite superficial at first, 
but may penetrate the deeper planes as they develop. They 
are often multiple and may be symmetrically arranged 
along nerve trunks. They have also been found on the 
mucous membranes. The multiple xanthomata often are 
large in size, measuring 3 or 4 cm. in diameter, are covered 
with freely movable skin through which bright orange-yel- 
low tumor substance can be seen. The color is due to a lipo- 
chrome of as yet unknown nature. The tumors are gen- 
erally discrete if not encapsulated; the cut surface shows 
a loose fibrous structure of a bright orange color; and on 
scratching with a knife, a greasy yellow material can be 
removed. In the subcutaneous tissue near the tumor, pro- 
jections of this yellowish material can sometimes be made 
out by the naked eye. This is an extension of the degene- 
rative process to the connective tissue in the tumor region, 
possibly along the lines of the lymph-channels.^ When 

iPollitzer: New York Med. Jour., 1899, Ixx, 73. 

2Hoessli: Xanthomata of the skin and the tendons. Beitr. z. klin. 
Chir., 1914, xc, 168. 

spollitzer and Wile: Jour. Cutan. Dis., 1912, xxx, 235. 

76 



frozen sections of such a tumor are examined with a polar- 
izing microscope, abundant doubly-refracting fat globules 
can be found chiefly in the cells, showing that much, though 
not all, of this fat is a cholesterin-ester. In fresh sections 
and also in those which have been preserved in formalin, 
many sheaves of fatty acid crystals may be present in the 
tissue. The structure of the nodules of xanthoma diabeti- 
corum is quite similar to those of multiple xanthomata. 

Closely related to the xanthomata are the so-called 
foam-cell tumors^ which occur about the jaws and in the 
substance of the tongue. In the tongue the fatty degenera- 
tion of the muscle fibers which form the tumor is quite 
well marked, a condition to which attention has been called 
in connection with the eyelid tumors.^ 

The xanthomata are in general perfectly benign 
tumors and in some instances have been known to dis- 
appear, though in a few instances sarcoma-like changes 
have been noted.^ 

The diagnosis is usually easily made by gross exami- 
nation and confirmed by the use of the polarizing micro- 
scope; and the employment of fat strains such as Sudan 
III or Scharlach R demonstrates a large amount of fat in 
the cells of the tumor.^ The association of the xanthomata 
with conditions in which the lipoid content of the blood 

iSick: Virchows Arch. f. path. Anat., 1905, clxxix, 550. Smith, C: 
Surg-., Gynec, and Obst., 1912, xiv, 551 (bibl.). 

2Pollitzer: New York Med. Jour., 1899, Ixx, 73. 

^Borst: Die Lehre von den Geschwiilsten, Wiesbaden, 1902, p. 125; 
Beneke: Miinchen. med. Wchnschr., 1909, Ivi, 1209; T^^'eil: Beitr. z. klin. 
Chir., 1914, xciii, 617; Landois and Reid: Beitr. z. klin. Chir., 1914, xcv, 
56. (A 58-year-old woman had a tumor on the dorsum of the foot for 
fourteen years. The tumor was the size of a fist, soft, and movable. 
It was encapsulated in thin connective tissue, but had grown into the 
tendon sheaths and penetrated between the bones of the ankle. On 
section it was a dark reddish brown, with yellow areas. Fresh prepara- 
tion showed typical xanthoma cells, as well as round cells, spindle cells 
with and without pig-ment, and giant cells of a myeloplaque type.) 

*Eisenbrey: Proc. New York Path. Soc, N. S„ 1915, xv, 70; Sike- 
meyer: Frankfort. Ztschr. f. Path., 1913, xiv, 428; MacFarland and Mc- 
Connell: Jour. Med. Research, 1904, N. S., vii, 69; Pinkus and Pick: 
Deutsch. med. Wchnschr., 1908, xxxiv, 1426; Schulte: Zeiglers Beitr., 
1916, Ivi, 570 (bibl.). Stelwag-en: Diseases of the Skin, 8th ed., Philadel- 
phia, 1916, p. 697. 

77 



is increased, such as jaundice, hepatic disease, diabetes, 
and pregnancy, suggests the reason for the deposition of 
excess lipoid in connective tissue.^ Hereditary hability has 
been noted in a few instances. 



CHONDROMA 

Tumors which consist of cartilage are called chondro- 
mata. They are usually lobulated, sharply circumscribed, 
and surrounded by a fibrous tissue capsule carrying a 
moderate number of blood-vessels. They are often multi- 
ple,2 occur chiefly in early life, and are usually of slow 
growth and benign, though in rare instances they may be 
malignant. 

Chondromata attached to areas where cartilage nor- 
mally occurs were designated by Virchow as ecchondro- 
mata. The ecchondromata are found as very irregular 
prominences on the inner surface of the symphysis pubis 
and the intervertebral disks of the spinal column. They 
grow also from the joints, the epiphyses, the costochondral 
junction of the ribs, and the inner surface of the larynx^ 
and trachea, and are usually surrounded by the normal 
perichondrium. While they usually remain small and prob- 
ably represent a hyperplastic process rather than a neo- 
plastic one, they occasionally form large tumors. 

Enchondromata are true cartilaginous tumors arising 
from tissues where cartilage is not normally found. They 
are perhaps most frequently met with on the phalanges 
and on the metacarpal and metatarsal bones, and are seen 
occasionally on the shafts of the long bones, in or about the 

^Schiller: Surg-., Gynec, and Obst., 1919, xxix, 450. See, however, 
Rosenbloom: Arch. Int. Med., 1913, xii, 395. 

2Ashhurst: Ann. Surg-., 1916, Ixiii, 167 (bibl.); Ohkubu: Arch. f. 
Entwcklngsmechn. d. Org-an., 1908, xxvi, 509 (bibl.), 

^Carroll: Ann. Otol. Rhinol., and Laryngol., 1911, xx, 807 (bibl.). 

78 



joints,^ and involving the bones of the pelvis and scapula.^ 
In these situations they form irregular lobulated tumors 
which erode and occupy a portion of the bony substance 
and push out the periosteum. The pelvic and scapular 
types often grow rapidly and the former, owing to the 
obstruction caused by their position, are clinically malig- 
nant. The tumors which are attached to bones are probably 
derived from fragments left during the normal formation 
of bone from cartilage during intrauterine life. Tumors 
composed of yellow fibro-elastic cartilage are chiefly noted 
as congenital spurs in the region of the ear, and on the 
lateral aspect of the neck,^ and are probably branchioge- 
netic in origin.* The tonsil often contains small areas of 
cartilage which may calcify and form bone and even 
marrow.^ 

Macroscopically, the tumors are usually sharply en- 
capsulated by a perichondrium, though in the softer types 
this is often missing. The cut section is translucent and 
bluish, and shows no bleeding points as the vessels are 
carried in the capsule and interlobular septa. Fibro-elastic 
cartilage is firmer and less friable than the hyaline variety, 
and is of a yellowish color. 

Microscopically, both the ecchondromata and the en- 
chondromata show a structure approximately that of the 
normal cartilage, that is, a clear basement substance 
staining blue with hematoxylin, with small oval or round 
cartilage cells with one or more nuclei lying in a clear area 

lEden: Arch. f. klin. Chir., 1914, civ, 277. 

^Walder: Deutsch. Ztschr. f. Chir., 1881, xiv, 305; Deganello, U., 
Virchows Arch., 1902, clxviii, 265; Nasse, Samm. klin. Vortr., 1895, N. F. 
124 (bibl.). 

3Zahn, W.: Virchows Arch., 1889, cxv, 47: Bidder, A.: ibid., 1890, 
cxx, 194; Wood, F. C: Ann. Surg-., 1904, xxxix, 57; Furstenheim: Jahrb. f. 
Kinderheilk., 1895. xl, 248. 

^Kolaczek: Beitr. z. klin. Chir., 1910, Ixviii, 120; Merkel: Die Gesch- 
wiilste d. Kindesalters, Handb, d. allg. Path, und d. path. Anat. d. 
Kindesalters, T^iesbaden, 1912, i, 368. 

^Cary, E. G.; Proc. New York Path. Soc, 1916, xvi, 173; Haberer: 
Arch. f. klin. Chir., 1909, Ixxxix, 782. 

79 



of capsule.^ Not infrequently, however, portions of the 
tumors show a tendency to the development of fibrous 
tissue, and the cartilage cells are not encapsulated, but be- 
come more or less irregular and send out prolongations 
into the surrounding tissue. Softening is not infrequent 
and may lead to the formation of cysts. Calcification is 
often seen, as is also the production of bone. Very few 
of the chondromata are composed wholly of cartilage, as 
there is usually more or less connective tissue which pene- 
trates between the different lobules of the growth. 

Cartilage very frequently forms a portion of the com- 
plex tumors seen in the pharynx, the region of the salivary 
glands, the breast, the kidney, the ovary, the uterus, and 
the testicle. These tumors, however, are never composed 
wholly of cartilaginous tissue, but contain myxomatous 
portions and areas of embryonic connective tissue. Occa- 
sionally muscular, and usually epithelial elements are also 
present. The details of some of the tumors of this type 
will be discussed in the section devoted to the teratomata. 

The diagnosis can usually be made clinically. The 
Roentgen ray gives valuable information concerning the 
central bone enchondromata, but if softening has occurred 
the presence of osteitis fibrosa must be eliminated by mi- 
croscopic examination. Edematous and encapsulated fibro- 
mata of the subcutaneous tissue may show the same trans- 
lucent bluish color as a chondroma and require microscopic 
differentiation. The chondrosarcomata and the osteochon- 
drosarcomata are, as a rule, not encapsulated, and are much 
more vascular than an ossified chondroma, but may on 
occasion be confusing. 

The clinical course is usually, as has been said, that of 
a benign growth, but as the tumor progresses it may press 

^For details of histology, see Spuler, R.: Zieglers Beitr., 1902, xxxii, 
253; Ernst, P.: ibid., 1905, xxxviii, 67; Merkel, H.: ibid., 1908, xliii, 485. 

80 



on an important organ or give rise to a spontaneous frac- 
ture. In a fe'.y ii^rinances, a chondroma has shown malig- 
nant qualities, though still retaining the morphology of 
cartilage.^ 

CHORDOMA 



The chordomata are extremely rare tumors which 
originate in remnants of the notochord.^ In man the noto- 
chord disappears early in embryonic life, the only trace of 
it being in the soft tissue of the intervertebral disks in 
children, and small masses which are found at the base of 
the brain in the clivus, just posterior to the sella turcica. 
These tumors, which are very rare, only some twenty hav- 
ing been recorded, occur anywhere along the spinal axis 
from the sella to the sacrum. They may be benign (six 
cases) and merely push aside the tissues with which they 
come in contact, or they may be malignant (twelve cases) 
and form metastatic deposits elsewhere in the body from 
the site of their origin. In one instance a tumor of the 
sella had penetrated the roof of the pharynx.^ In another 
it had extensively involved the brain.* In gross appear- 
ance the tumor is jelly-like, being composed of clear, trans- 
parent masses, which in many instances have been diag- 
nosticated originally as chondromata, myxochondromata, or 
even gelatinous carcinomata, and only on more careful 
study recognized as derived from notochordal tissue. 

Microscopically the tumor is composed of structureless 
gelatinous tissue, staining with basic dyes and containing 

iFrangenheim: Beitr. z. klin. Chir., 1911, Ixxiii, 226. 

^For a discussion of the orig-in of the cells of the notochord, see 
Huber: Anat. Rec, 1918, xiv, 217; and B. F. Kingsbury: Science, 1920, 11, 
190. Huber considers the tissue entodermal in origin, and Kingsbury 
mesodermal. 

sLinck: Zieglers Beitr., 1909, xlvi, 573. 

^Jelliffe and Larkin: Jour. Nerv. and Ment. Dis., 1912, xxxix, 1. 

81 



but few cells or none at all, while in this lie areas of large, 
clear, blister-like cells resembling superficially those of the 
normal hyaline cartilage, but much more irregular in their 
size and shape. The cells frequently disappear, leaving 
large areas composed solely of a structureless, jelly-like 
material. In the malignant tumors the resemblance to 
notochordal tissue is much less close than in the benign 
form.^ 

OSTEOMA 

An osteoma is a tumor consisting of bone tissue. Mere 
calcification of a tissue is not sufficient to permit of the 
diagnosis of osteoma; the presence of bone cells is a pre- 
requisite. Included with the bony tissue in an osteoma may 
be in addition to the bone cells and Haversian canals, 
periosteum, perichondrium, cartilage, and occasionally mar- 
row; all elements which may be present in a true osteoma. 
Two types of osteoma are a compact, hard, ivory-like, or 
eburnated variety, and a softer, fibrous, spongy, or medul- 
lary kind. 2 

It is often difficult to distinguish true bony tumors 
either macroscopically or microscopically from those osse- 
ous masses which arise so frequently after trauma and 

^For further details see H. Albert: Surg., Gynec, and Obst., 1915, 
xxi, 766. Feldman: Zeiglers Beitr., 1910, xlviii, 630; Frenkel and Bassai: 
Arch, de med. exper. et d'anat. path., 1910, xxii, 703; Mazzia: Centralbl. 
f. allg-. Path. u. path. Anat., 1910, xxi, 769; Wood: Proc. New York 
Path. Sec, 1913, N. S. xiii, 103; Vecchi: Arch. f. klin. Chir., 1912. xci, 
575; Daland: Boston Med. and Surg. Jour., 1919, clxxx, 571 (bibl.); 
Lund: ibid., 1919, clxxxi, 704. 

^The student will find many details concerning osteomata in the 
text books on surgery, especially in Schuchardt, Knochen und Gelenke, 
Deutsche Chir., 1899. Among other references which may be of interest 
are Cornil and Coudray, Osteomes musculaires. Rev. de Chir., 1907, 
xxxvi, 669; Rothschild: Ueber myositis ossificans traumatica, Beitr. z. 
klin. Chir., 1900, xxviii, 1; Housell: Traumatische Exostosen, Beitr. z. 
klin. Chir., 1898, xxii, 2*77; Uyeno: Osteofibromata of the superior 
maxilla, Beitr. z. klin. Chir., 1909, Ixv, 301; Elliott, A. R.: Myositis ossi- 
ficans. Jour. Am. Med. Assn., 1911, Ivii, 873 (bibl.); Eckert: Osteomata 
of the inferior maxilla, Beitr. z. klin. Chir., 1899, xxiii, 674; Frangen- 
heim: Osteitis fibrosa des Schadels, Beitr. z. klin. Chir., 1914, xc, 117. 

82 



chronic inflammation. The name osteoma should therefore 
be reserved for such growths as are formed independently 
of any known cause and in a region where bone is not 
normally present. The bony tumors seen about tubercu- 
lous processes in bone, or chronic ulcerations due to vari- 
cosities of the lower extremity, those produced after long 
continued irritation of trauma, such as "rider's bone," the 
osseous tissue occurring in the muscles after chronic in- 
flammation or trauma (myositis ossificans), the osteophytes 
about the joints in rheumatoid arthritis, bone produced in 
the kidney by ligation of the renal artery, etc., these all 
really belong in a separate group and should not be re- 
garded as true osteomata. 

The osteomata are dependent for their formation upon 
the activity of the cells of the periosteum, perichondrium, 
or cartilage, forming the basis of a tumor, for true bony 
tissue is incapable of growth, calcification taking place 
after the production of an osteoid tissue from the medulla, 
periosteum, or cartilage. Osteomata originate on a carti- 
laginous substrate more frequently than on periosteum or 
other fibrous tissue structure. 

If the tumors project from the surface of the bone 
they are designated exostoses; if from the interior or the 
medulla enostoses. Bony tumors are naturally most fre- 
quently found in the skeletal structures ; but true osteomata 
have been observed in the brain, in the meninges, in the 
trachea and lung, in the bronchial lymph-nodes, in the 
parotid, in the cavernous tissue of the penis, in the eye, 
in the skin of old people, and in the fibrous thickening of 
elephantiasis, though as compared to the skeletal tumors, 
osteomata in these situations are rare. The very infre- 
quent multiple exostoses of the skeleton are closely related 
to the m.ultiple chondromata, and like them they appear 
congenitally or in early youth. They grow slowly and form 
nodular tumors, usually flat, but occasionally pedunculated. 

83 



They often have cartilaginous portions and like the chon- 
dromata are found chiefly at the end of the long bones, 
especially in the metaphyses. Occasionally, they appear in 
the joints. As the bone grows their position changes and 
they are found then on the diaphyses, usually accompanied 
by some alteration in the normal form of the bone. They 
occur, also, in the skull, both on the external and internal 
surfaces, and are not infrequent on the bones of the fingers 
and toes. They have also been noted on the scapula and 
the bones of the vertebral column. 

The true fibrous exostoses are usually very white and 
ivory-like, though occasionally spongy types are seen. They 
occur most often on the skull, in the antra of the face,^ and 
on the jaw, but are not infrequent under the nails of the 
toes, the subungual osteomata. On the skull, the tumors 
are frequently multiple and may cause serious injury to the 
brain by pressure. 

All of the bony tumors are extremely slow growing 
and benign in their course, unless they happen to encroach 
upon some important organ. 

Bony tissue may also compose a small portion of the 
mass of a chondroma, forming an osteochondroma; or of a 
fibroma, forming an osteofibroma, and such tissue is not 
infrequent in the complex tumors of the parotid, the mam- 
mary, and the genitourinary apparatus, especially in the 
dermoid cysts of the ovary, which are really teratomata. 
The osteosarcomata will be discussed under sarcoma. 

There are a number of general diseases in which bone 
formation takes place in unusual sites; among these are 
myositis ossificans progressiva, which consists of a multi- 
ple progressive ossification of the muscle tissue and tendons 
connected to them, spreading occasionally to the fascia. 
The appearance of the bone is preceded by inflammatory 

^Culbert, W. K: Multiple osteoma of the nasal accessorj^ sinuses, 
New York State Jour. Med., 1918, xviii, 465 (bibl.). 

84 



reaction in the tissues in which it takes origin, and the 
disease is usually accompanied by febrile attacks with 
swelling and tenderness of the muscles attacked. The 
onset is usually in the earlier years of life, and may be 
progressive so that many of the muscles are entirely stif- 
fened, producing the so-called ossified men. Nothing is 
known of the causation. 

A somewhat similar lesion is seen in the local myositis 
ossificans, which, however, follows directly upon traumatic 
injury or overstraining of a muscle. This results in the 
formation of a small or large mass of bony tissue in the 
structure of the muscle. In this same group are the rider's 
bone of the adductor muscles, and the exercise bones which 
are seen in the pectoralis, deltoid, and biceps muscles of 
athletes. 

The types of new growth of bone known as osteitis 
deformans,^ osteitis fibrosa, and leontiasis ossea belong in 
the class of hyperplasias and are probably not neoplastic in 
nature. In this group, perhaps, may also be included the 
hypertrophies which occur in acromegaly. Occasionally in 
osteitis deformans or osteitis fibrosa a tumor-like process 
may ultimately develop, the type being that of a giant-cell 
sarcoma. 

ANGIOMA 

The angiomata may be of two varieties, one containing 
an excess of blood-vessels, the hemangiomata, the other 
containing an excess of lymph-vessels, the lymphangio- 
mata.- Combination forms are occasionally seen in the 

^Vogel: Med. Rec, Xew York: 1911, Ixxx, 214; Higbee and EUis: 
Jour. Med. Research, 1911, X. S., xix, 43 (bibl.). 

^Fischer, B., and Zieler, K., Lubarsch-Ostertag', Erg-ebn. d. allg'. 
Path., 1904-5, x, 815 (pathology of the angiomata) (bibl.). 

85 



skin. Usually the term angioma is limited to the type 
with an excess of blood-vessels. 

Hemangioma 

The most frequent form of the hemangiomata are the 
congenital, flat, reddish, areas so frequently seen on the 
skin and usually called naevi. These consist simply of 
groups of dilated capillaries which lie in the corium and 
are covered by a very thin layer of epithelium and sur- 
rounded by connective tissue. When the tumors project 
from the surface they usually contain a considerable 
amount of newly formed connective tissue in addition to 
the dilated vessels, and the walls of the capillaries are 
thicker than in the nsevi. Growth may take place by the 
formation of new vessels and the penetration of the sur- 
rounding fat and connective tissue. Partial or complete 
regression is sometimes seen, due to thrombosis of the 
vascular sinuses. 

The largest angiomata, which are usually called 
cavernous angiomata, often form tumors of considerable 
size, and are found on the lips, the skin of the face, tongue, 
and extremities, and occasionally in the muscles,^ or in the 
internal organs, such as the spleen,^ liver, kidney, and 
uterus. They may be single or multiple.^ They are com- 
posed almost entirely of greatly dilated vessels with only 
a moderate amount of connective tissue between the blood 
filled sinuses. The individual tumors vary considerably, 
however, in the relative space occupied by vessels and in- 
terstitial tissue. 

When occurring in the osseous system,* these tumors 

^Muscatello: Virchows Arch, f. path. Anat., 1894, cxxxv, 277. 
2Dowd: Cavernous ang-ioma of spleen, Ann. Surg., 1915, Ixii, 177. 
'Hildebrand: Deutsch. Ztschr. f. Chir., 1890, 1, 91. 
*Schone: Zieglers Beitr., 1905, Suppl. vii, 685. 

86 



are capable of causing erosion of the bone and occasionally 
seem to have the power of progressive growth.^ While 
generally considered as perfectly benign, types have been 
observed which formed metastases. ^ 

Cavernous angiomata are extremely frequent in the 
liver. The growths are unquestionably due to a congenital 
lack of development of the walls of the blood-vessels. They 
may be accompanied by malformations in the organs. Re- 
gressive changes may take place with thrombosis of the 
vessels and the ultimate formation of masses of fibrous 
tissue. 

In some types, which may be properly designated 
hypertrophic angiomata, the tissue consists almost ex- 
clusively of thick-walled capillaries, the latter usually sur- 
rounded by a considerable layer of adventitial cells. When 
the blood has escaped from such a tumor and the vessels 
have been shrunken from the action of the fixative em- 
ployed, the cellular types resemble somewhat in structure 
an adenoma of the sweat glands, or one of the congenital 
moles. If the adventitious cells are very abundant the 
microscopical picture may often suggest a sarcoma. The 
clinical history of the patient is very important in making 
a differential diagnosis, but usually it is possible by careful 
microscopical examination to find the contracted capillaries 
and to observe that the cells are not in as intimate relation 
with the capillary walls as is usual in the angiosarcomata. 
The absence of mitotic figures in the adventitia cells speaks 
for angioma and against sarcoma. Transition cells between 
the true angiomata and tumors containing a large amount 
of fat tissue are not infrequently seen. These may be 
designated as fibroangioma or lipoangioma. The propor- 
tions of the fat or fibrous tissue to the vascular tissue 

iMuthmann: Virchows Arch. f. path. Anat., 1903, clxxii, 324 (bibl.). 

^Borrmann: Zieglers Beitr., 1907, xl, 372; Shennan: Jour. Path, and 
Bacteriol., 1914-15, xix, 140; Ewing": Neoplastic Diseases, Philadelphia, 
1919, p. 223. 

87 



must determine whether the tumor shall be called a vas- 
cular lipoma or a vascular fibroma. The angiosarcomata 
will be discussed under the general heading of sarcoma. 

The adenomata are easily differentiated from the cellu- 
lar vascular tumors because there is no membrana propria 
about the cellular interstitial tissue in the angiomata, while 
in the adenomata such a membrane is always present. Such 
confusion is not apt to arise in the cavernous forms of 
angioma because there, as the vessels form a large part 
of the tissue and the cells a relatively unimportant por- 
tion, the diagnosis is easy. 

Many angiomata, especially those of large size, are 
unquestionably due to a congenital malformation of the 
tissues with overproduction of vessels and capillaries; 
though they often make their appearance at a period con- 
siderably after birth. W. Wolf found that in persons under 
twenty years, 56 per cent, showed angiomata, whereas in 
older people, 74 per cent, showed these tumors, usually of 
small size. 

Lypmhanigoma 

A much rarer type of tumor, but one of much the 
same architecture as the previous form, is the lymph- 
angioma in which instead of dilated blood-vessels, the 
sinuses are lymph-spaces. These spaces are filled with a 
clear serous fluid or lymph, or contain a large number of 
lymph-cells. The dilated vessels consist merely of fibrous 
tissue lined with endothelial cells, though their walls may 
contain muscle fibers. The interstitial connective tissue 
may be abundant or scanty, and often contains collections 
of lymphoid cells. The lymphangiomata may be flat,^ like 

^Details of these skin forms which include the lymphangioma cutis 
circumscripta and lymphang-ioma tuberosum simplex of the dermatolo- 
gists may be found in the dermatological texts, such as Darier, English 
edition, 1920; Stelwagon, H. W., Treatise on Diseases of the Skin, 8th 
ed., Philadelphia, 1916, p. 690. 

88 



the simple hemangiomata, or they may be composed of 
large cystic cavities,^ or they may form firm tumors. 
Usually the lymphangiomata contain a moderate amount of 
fat tissue which may in certain cases be so abundant as to 
warrant the appellation of lymphangiolipomata ; this is 
especially true of the retroperitoneal tumors.^ The chronic 
thickenings of the skin with the formation of much fibrous 
tissue, which were mentioned as a sub-type of fibroma bear- 
ing the clinical designation of elephantiasis, are often char- 
acterized by extensive hyperplasia and dilatation of the 
lymph-vessels of the affected region. 

Certain of the angiomata of the tongue and cheek 
known as macroglossia and macrocheilia are undoubtedly 
lymph-angiomatous in nature. Usually these tumors are 
quite benign, though a sarcomatous transformation of a 
cavernous lymphangioma has been observed. 

Other types are the chylangioma produced by dilata- 
tion of the lacteal vessels in the intestine and mesentery^ 
and the rare hygroma colli cysticum occurring on the 
lateral aspects of the neck.^ The sacral hygromata may 
be occasionally composed of lymph cysts but are usually 
more closely related to the meningoceles.^ 

While the basis for most of the lymphangiomata is 
some congenital malformation, yet stasis in the previously 
formed vessels is responsible for the increase in size ob- 
served in many of these tumors, and another factor is the 
new formation of vessels by growth. 

The diagnosis is usually not difficult, and in the coarse 

^Fischer and Zieler: Lubarsch-Ostertag-, Brgebn. d. allg. Path., 
1904-5, X, 842; Herxheimer and Schmidt, ibid; 1912, xvi^, 636. For a 
clinical discussion, see Winslow, Surg-., Gynec, and Obst., 1917, xxv, 
428. 

^Takano and Hanser: Zieglers Beitr., 1912, liii, 105; Steele; Am. 
Jour. Med. Sc, 1900, cxix, 311. 

sBlatteis: Proc. New York Path. Soc, 1910, x, 102; Thalhimer: Proc. 
New York Path. Soc, 1913, xiii, 5. 

^Nasse: Arch. f. klin. Chir., 1889, xxxviii, 614. 

^Borst: Centralbl. f. allg. Path., 1898, ix, 449. 

89 



cystic forms is often easier on gross than on microscopic 
examination, especially as the endothelial lining is apt to 
be destroyed either from pressure atrophy or infection. 
The contents of the large cysts may be clear, cloudy, or 
blood-tinged. Cholesterin crystals, blood pigment, fatty 
degenerated cells, and leucocytes are often present. The 
solid tumors require microscopical examination for the de- 
termination of their nature. The sinuses contain clear 
fluid which coagulates on fixing and usually contains a few 
leucocytes. The sources of error are either that the blood 
may escape from the sinuses of a hemangioma during 
operation, or that, owing to thrombosis, areas of capillaries 
may be cut off and the blood which they contained be ab- 
sorbed, leaving only clear fluid; so that a hemangioma 
may be considered a lymphangioma. On the other hand, 
lymph-sinuses may be filled with blood due to operative 
trauma. 

SARCOMA 



The sarcomata are malignant tumors derived from the 
various connective or supporting tissues of the body. Their 
classification into varieties depends upon the amount of the 
connective tissue stroma, upon the relationship of the tumor 
cells to the blood-vessels, upon the type of interstitial tissue, 
whether fibrous, bony, or cartilaginous, in some groups, 
upon the size and shape of the cells which compose the 
tumor, or, finally, upon certain chemical properties of the 
cells which lead them to produce pigment, as in melano- 
sarcoma, or chloroma. In addition, the basis for classifica- 
tion may be on the histological origin of the tumor cells, 
as in the plasmomata or in the myelomata. 

Sarcoma is rarer than carcinoma, the proportion being 
about one to ten. It is m.ost frequent in the upper age 

90 



groups, as is carcinoma, but sarcoma is more often congen- 
ital, and is also more evident in the first few years of life, 
although the total number of tumors thus seen is small.^ 
The tumor occurs in all the tissues of the body, and is most 
frequent in the skin, subcutaneous and subserous connec- 
tive tissues, the fasciae, the marrow and substance of the 
bones, and the choroid coat of the eye. A fairly common 
site is the uterus and the ovary. Certain special types de- 
velop in the dura mater, the brain and spinal cord, the 
kidney, the adventitia of the blood-vessels, the sheaths of 
the nerves, and the submucous tissue. The lymphoblasto- 
mata originate in the lymph-nodes or in the diffuse lymph- 
oid tissues of the body. 

The highly cellular character of most of the sarcomata 
and the close relationship to the vascular channels which 
the cells possess make these tumors, on the whole, the most 
malignant variety, surpassing in this regard most of the 
carcinomata. Especially is this true of the lymphosarco- 
mata and the melanosarcomata. On the other hand, some 
of the slow growing fibrosarcomata are scarcely to be dis- 
tinguished from a rapidly proliferating fibroma, and the 
giant-cell sarcomata of the bones and those of the ramus 
of the jaw (epulis) are comparatively benign. The rapidly 
growing forms are very liable to degeneration, ulceration 
and hemorrhage, because the imperfectly formed vessels 
are easily ruptured by the slightest trauma and the cells 
often reach a point where the circulation is insufficient to 
maintain their growth, so that they die of innutrition. 

iWelnberg- and Gastpar: Ztschr. f. Krebsforsch., 1904, ii, 216, 220; 
1906, Iv, 18; Bashford and Murray: Second Sci. Report, Imperial Cancer 
Research Fund, London, 1905, i, 24; Roger Williams: Natural History 
of Cancer, New York, 1908, p. 322; Weller: Arch. Int. Med., 1915, xv. 
518; Harbitz and Platou: Norsk. Mag. f. Lsegevidensk., 1917, Ixxxviii, 
145 (Abstr. in Jour. Am. Med. Assn., 1917, Ixviii, 1074). 

91 



Metastasis is more apt to occur through the vascular sys- 
tem than through the lymph system, in contrast to carci- 
noma, and in consequence the regional lymph-nodes are in- 
vaded much less often than by the epithelial malignant 
tumors. 

Spindle-Cell Sarcoma 

The sarcomata arising in the fibrous connective tissue 
usually possess cells of a spindle shape which give rise to 
the name of this particular type of tumor. The cells may 
be large, as in large spindle-cell sarcoma, or small, as in 
small spindle-cell sarcoma. A variety with short spindle 
cells has been given the descriptive name of "oat-cell" 
sarcoma, but possesses no other characteristics which would 
warrant its differentiation from the preceding. A spindle- 
cell sarcoma may be composed alm^ost entirely of the char- 
acteristic cells or may contain so large an amount of fibrous 
connective tissue that the differentiation between the malig- 
nant form and a richly cellular fibromia is difficult. Usually, 
however, some portion of the sarcomatous mass will show 
characteristic areas in which a large number of cells are 
closely crowded together without much interstitial tissue, 
frequently with mitotic figures in the nuclei, which reveal 
the presence of a malignant growth. The cells are usually 
arranged in bundles, lying parallel to the blood-vessels and 
surrounding them, and thus forming a wavy or intricate 
pattern. In microscopic sections taken at random through 
a tumor, cells will be found which are cut either longitudin- 
ally or transversely, or in various intermediate positions, 
and consequently will have either a circular, an oval, or a 
cylindrical outine. The consistency of such a tumor depends 
entirely upon the proportion between the fibrous tissue and 
the cellular constituents. The fibrosarcomata approach the 

92 



fibromata in firmness, whereas the very cellular spindle- 
cell sarcomata are soft and elastic. The cut surface shows 
like variations, depending on the composition of the tissue. 
The fibrosarcomata are firm, glistening, white, because of 
the infrequency of the blood-vessels ; while the very cellular 
forms are yellowish or pinkish, depending on the vascular 
supply, are somewhat more opaque than the fibromata, and 
often show an abundance of punctate hemorrhages from 
the sectioning of the small vessels. A capsule is usually 
present in the earlier stages of the spindle-cell sarcomata, 
due to the expansive nature of the growth which presses 
aside the connective tissue in which it has arisen; and not 
infrequently tumors of this type may be fairly easily shelled 
out of their connective-tissue surroundings. Later, as the 
tumor gains in growth capacity, it penetrates the capsule 
and infiltrates the surrounding tissue and is no longer 
sharply delimited. Nevertheless, it should alw^ays be re- 
membered, especially in the slow growing subcutaneous 
tumors, that the capsule may long remain and give rise to 
an erroneous clinical diagnosis. 

The spindle-cell sarcoma is the most frequent type and 
occurs usually in the bones, periosteum, subcutaneous 
tissue, and muscles, but is seen also in many of the organs, 
such as the uterus, ovary, mamma, testis, thyroid gland, 
etc. The lobulated form, early invasion of the skin, growth 
rate, and soft consistency of the fibrosarcomata usually 
separate them from the fibromata. The periosteal types are 
less easy to diagnose and rarely may be multiple.^ When 
situated in the skin, the fibrosarcomata must be differen- 
tiated from infectious granulomata, granulation tissue, 
mycosis fungoides, and diseases of a different type, such 
as Hodgkin's disease or leukemic nodules. 

Microscopically, the differentiation of a fibrosarcoma 

^Nasse: Virchows Arch. f. path. Anat., 1883, xciv, 461, 

93 



from an infectious granuloma, granulation tissue, mycosis 
fungoides, or leukemic nodules, is not, as a rule, difficult. 
The cells of mycosis fungoides are apt to be small and 
round, and spindle cells are not numerous. The different 
types of infectious granulomata are usually to be distin- 
guished, if sufficient care is taken, by the demonstration 
of the specific organism. The club-shaped forms of actino- 
mycotic granules are easily identified; and the differentia- 
tion of the spherical and budding yeasts in blastomycosis 
is not difficult, especially if they are included in giant cells. 
Sporotrichosis is sometimes hard to diagnose, but slough- 
ing and extensive invasion of the tissues with leucocytes 
of various types are more suggestive of granuloma than of 
sarcoma; and the clinical picture is not that of sarcoma. 
Simple granulation tissue is often edematous and rarely 
as cellular as a sarcoma. The history is of value, unless 
the wound follows the removal of a sarcoma, in which case 
differentiation from a small specimen may be impossible. 
Leukemia is immediately differentiated by a blood count; 
and in Hodgkin's disease the characteristic large endothe- 
lial multinuclear cells will permit a diagnosis. The neurofi- 
bromata are frequently considered to be sarcomata, but 
without justification. They are, it is true, fairly cellular, 
but mitoses are absent and there is a peculiar spongy look 
to the tissues and an absence of broad collagen bundles, 
which, together, with the occasional presence of bundles of 
nerve fibers will help in the differentiation. A history of 
pain on pressure of the nodule, or the presence of similar 
nodules symmetrically distributed along a nerve trunk are 
valuable aids in differentiation. Keloids can be excluded 
by the extreme density of the collagenous bundles and the 
scarcity of nuclei. 

The greatest difficulty lies in differentiating between 
the soft fibromata of the skin and subcutaneous tissues and, 

94 



rarely, of other organs, and the fibrosarcomata of low po- 
tential malignancy. There may be no difference in the 
amount of connective tissue present in the sarcomata; the 
nuclei of the cells are, on the average, more variable in 
size and in the amount of chromatin; very large nuclei or 
lobulated nuclei are occasionally seen. Mitoses are fairly 
abundant in sarcoma, but absent in fibroma. In a doubt- 
ful case, a large number of sections should be made from 
different portions of the growth in order to determine if 
there are not areas, especially about those parts which 
have the best blood supply, the cellular richness of which 
will show that the tumor is a sarcoma. Despite all pre- 
cautions, however, mistakes will occur, and the writer has 
seen a few tumors of exactly similar morphology, the ulti- 
mate history of which has necessitated the diagnosis of 
sarcoma in some, and in others the diagnosis of fibroma. 
Fortunately, however, such difficult situations are rare; 
most of the fibrosarcomata can be diagnosticated with a 
little care and the study of a few sections. 

Osteosarcoma- 

Tumors containing bone may spring from the bone or 
periosteum, from the joint capsules,^ or even from the 
fascia.* Very rarely they may occur in other places, such 
as the mamma," though they are frequent in the breasts 

2Buerg'er: Surg-., Gynec, and Obst., 1909, ix, 431; Am. Jour, Med. Sc, 
1910, cxl, 355; Gross: Am. Jour. Med. Sc, 1879, Ixxviii, 17; Bloodgood: 
Ann. Surg-., 1910, lii, 145; 1912, Ivi, nO. 

sRydygier: Deutsch. Ztschr. f. Chir., 1906, Ixxxii, 211; Moser: ibid., 
1909, xcvili, 306. 

^Hammer: A malig-nant fascial giant-cell sarcoma, with bone forma- 
tion, Beitr. f. klin. Chir., 1901, li, 527. 

^Bland-Sutton: Archives of Middlesex Hospital, 1910, xix, 98; Heuter 
and Karrenstein: Virchows Arch. f. path. Anat., 1906, clxxxiii, 495; St. 
Arnold, ibid, 1897, cxlviii, 449. 

95 



of old dogs. An ossifying sarcoma has also been seen in 
the thyroid.^ 

Osteosarcomata are most frequent in the shafts of the 
long bones, favorite sites being the lower end of the femur 
and the upper end of the tibia. Both extremities of the 
humerus seem equally susceptible as locations. The epiphy- 
sis is often involved by extension, the joints less frequently. 
Most of the tumors arise in the endosteum or substance 
of the bone and either extend along the marrow cavity and 
shaft or expand the latter into a thin shell, which crackles 
when firmly palpated. A periosteal origin is less frequent ; 
and the current tendency is to classify the tumors simply 
as central or peripheral in origin since the exact point of 
departure of the tumor is often difficult if not impossible 
of determination. 

Macroscopically, these tumors form spindle-shaped 
enlargements or irregular masses dilating the bone, the 
periosteum usually being distended by the tumor; and only 
late in the disease do the cells of the sarcoma break through 
the fibrous layer or the bony capsule surrounding the 
tumor. Many osteosarcomata are extremely hard and bony 
or of cartilaginous texture; some, however, are fairly soft 
except in the calcified areas; and a number contain myxo- 
matous tissue. On section, the tumor is usually of a dark 
red color and infrequently contains irregularly distributed 
hemorrhagic areas. It may be very firm and resist the 
knife, or it may be soft and cartilage-like, the so-called 
osteoid sarcoma. 

Microscopically, some of these tumors resemble very 
considerably a spindle-cell sarcoma and only in small areas 
contain any bony material. In others, the bone forms the 
most prominent portion of the tumor, and the tumor cells 

iPick: Ztschr. f. Heilk., 1892, xiii, 71; Funkenstein: Virchows Arch, 
f. path. Anat., 1903, clxxi, 34. 

96 



occupy spaces in the calcified tissue. Still other varieties 
have about an equal proportion of cellular material and a 
transparent osteoid structure of newly formed bone in 
which calcification has not been completed. In these tumors 
the cells are usually not spindle-shape, but polymorphous. 
Metastases, which are very frequent in the lung,^ vary with 
the complexion of the primary tumor. The amount of bone 
may be large or small, but usually there is much osteoid 
tissue and not much mature bone. This type is usually 
highly malignant, though examples are met with which 
progress very slowly and do not metastasize. 

Chondrosarcoma 

Chondrosarcoma is a type of sarcoma in which the in- 
terstitial tissue is composed of hyaline cartilage instead of 
bone or connective tissue. The amount of the cartilage 
may be so great that the sarcoma cells are difficult to find, 
and occasionally it is impossible to decide whether the 
tumor is a chondrosarcoma or a chondroma.^ True chon- 
drosarcomata arise in bone, are highly malignant, and 
should be carefully distinguished from the relatively benign 
complex tumors of the salivary glands which also contain 
cartilage. A more frequent type than pure chondrosar- 
coma is the osteo-chondro-sarcoma, or myxo-chondro- 
osteo-sarcoma.^ Tumors of this type occur in the soft 
parts more frequently than do the osteosarcomata or the 
chondrosarcomata. They are occasionally seen in the 
mamma, and have been described in the thyroid* and other 
organs of the body. 

iLeCount: Bull. Johns Hopkins Hosp., 1909, xx, 361. 
^Deganello: Virchows Arch. f. path. Anat., 1902, clxviii, 265. Nasse: 
ibid., 1883, xciv, 461. 

3Seitz: Deutsch. Ztschr. f. Chir., 1905, Ixxviii, 60. 
*Funkenstein: Virchows Arch. f. path. Anat., 1903, clxxi, 34. 

97 



Myxosarcoma 

This type of tumor has been mentioned under the 
heading of myxoma, and does not need further considera- 
tion here. It is an extremely malignant growth with a 
fairly cellular stroma which consists largely of myxomatous 
tissue. Such tumors occur most frequently in the skin and 
subcutaneous tissues ; but occasionally congenital forms are 
seen in the retroperitoneal spaces, where they form myxo- 
fibro-lipo-sarcomata or other complex types. 

Giant-Cell Sarcoma 

This is a special type of sarcoma arising from the 
marrow of the bone, and is hence often termed a myeloid 
sarcoma. These neoplasms may remain for a long time 
quiescent in the marrow cavity and only late penetrate the 
bone and appear on the surface. Usually they distend the 
bone as they erode, and form spindle or oval enlargements 
of the osseous substance. The x-ray picture of such a tumor 
is very characteristic. 

Macroscopically, they are very dark red on the cut 
surface, and contain a good deal of free blood and blood 
pigment, usually hemosiderin. The central portion of the 
tumor is very liable to necrosis, often followed by extensive 
hemorrhage ; and occasionally after the blood is absorbed a 
cyst remains with a wall of tumor about it.^ Occasionally 
these cysts are so abundant and extensive that it is difficult 
to trace any remaining tumor tissue, and doubt may arise 
as to the tumor nature of the disease, the cysts resembling 
those of osteitis fibrosa. When the hemorrhage has been 
very extensive the tumors have been described as bone 

^Nakayama: Beitr. z. klin, Chir., 1909, Ixiv, 524. 

98 



aneurysms, but they are really nothing but giant-cell sar- 
comata in which extensive hemorrhage has taken place.^ In 
this class belong the epulides of the jaw, in which hemis- 
spherical or nodular tumors arise usually from a cavity 
from which an old tooth has been removed, or from be- 
tween the teeth. They rarely erode the bone, and can 
scarcely be considered malignant, seventy out of seventy- 
two cases not recurring after operation. 

The most frequent site for the giant-cell sarcomata is 
the lower end of the femur and the upper end of the tibia. 
They occur also in the vertebral column and in other places, 
especially in the tendon sheaths,^ in most instances those 
of the forearm and hand. If many giant cells are present 
these tumors are relatively benign,^ but occasionally they 
are malignant, especially when round and spindle cells pre- 
dominate. Similar tumors have been found elsewhere, for 
instance, in the skin,* in the uterus,^ and in the intestine.^ 

Microscopically, these tumors vary a great deal. A 
number are composed of spindle and oval shaped cells with 
a very few giant cells. Others are composed almost en- 
tirely of giant cells. The first variety is usually more malig- 
nant; the second is apt to be benign, though in some in- 
stances local recurrences may be quite malignant. 

As an illustration of the lack of malignancy of a tumor containing 
numerous giant cells may be cited St. Luke's Hospital Path. No. 10618, 
which is a giant-cell sarcoma from the inferior turbinate bone. This 
patient has been operated on eleven times in the past eleven years, 
and is still in good physical condition. The tumor rej2urs very slowly, 

iQaylord: Ann. Surg., 1903, xxxvii, 834. 

2Fritsch: Beitr. f. klin. Chir., 1908. Ix, 344; Fleissig: Deutsch. 
Ztschr. f. Chir., 1913, cxx, 239; Speiss: Frankf. Ztschr. f. Path., 1913, 
xiii, 1; Bellamy: Jour. Path, and Bacteriol., 1901, vii, 465; Tourneux: 
Rev. de Chir., 1913, xxxiii, 785; Broders: Ann. Surg., 1919, Ixx, 574 
(bibl.). 

^Bloodgood: Ann. Surg., 1919, Ixix, 345; Barrier Ann. Surg., 1913, 
Ivii, 244; Barrie and Hillman: Surg., Gynec, and Obst., 1914, xix, 42; 
Martland: Proc. New York Path. Soc, 1915, xv, 119; Haussling and 
Martland: Ann. Surg., 1916, Ixiii, 545. 

*Zipkin: Virchows Arch. f. path. Anat., 1906, clxxxvi, 240. 

'Borrmann: Ztschr. f. Geburtsh. u. Gynak., 1900, xliii, 264. 

•Bokay: Virchows Arch. f. path. Anat., 1913, ccxiii, 249. 

99 



and shows no tendency to metastasize at a distance, though it has 
gradually invaded the superior maxilla. The type of the tumor remains 
practically the same throughout the course of years. The proportion 
between the giant cells and the stroma is fairly constant, the former 
predominating. Mitotic figures are fairly frequent in the giant cells. 

The giant cells, with but few exceptions, are of the 
type in which the nuclei are scattered throughout the cell 
rather than in the periphery. Occasionally, tumors are 
seen in which the Langhans' type of giant cell is found 
throughout the mass, the nuclei being arranged around the 
periphery of the large granular cell bodies.^ Mitotic figures 
are very rarely seen in the nuclei of the giant cells, except 
in rapidly growing or recurrent tumors. The giant cells 
frequently act as phagocytes for leucocytes and particles 
of bone and other material, such as blood pigment. 

The curious error is sometimes made of considering 
the chalazion as of the nature of a giant-cell sarcoma. In- 
stead it is a granulation tissue mass caused by inflamma- 
tion in and about the Meibomian glands of the eyelid. The 
presence of lipoid substances, and possibly of bacteria, 
though not, as was originally thought, of the tubercle 
bacillus, may give rise to giant cells in the reactive con- 
nective tissue. The growth is entirely benign, and can be 
cured by cutting into the mass and removing its contents. 

Angiosarcoma 

Angiosarcomata are sarcomata in which the blood- 
vessels dominate the morphology of the tumor, the cells 
being arranged around, often in close contact with, the 
thin-walled vascular tube, or even lining it. This type of 
neoplasm is only a morphological type of sarcoma, and does 
not differ in its qualities from the other forms, except as 
regards its high malignancy. 

iZipkin, R. : Uber Riesenzellen mit randstandigen Kernen in Sarko- 
men, Virchows Arch. f. path. Anat., 1906, clxxxvi, 240. 

100 



Alveolar Sarcoma 

This is another type in which the arrangement of the 
connective tissue gives the tumor a pseudoalveolar arrange- 
ment. Many of the mole tumors have this morphology. 

Round-cell Sarcoma 

Two types of sarcomata have received the descriptive 
name of round-cell sarcoma. One type is more correctly 
described under the name lymphoblastoma, growths derived 
from the lymphoid tissue of the body and made up of rela- 
tively small cells. The other type is a rare tumor, made 
up of much larger cells and found chiefly in the muscles, in 
the embryonal tumors of the testicle and ovary, and occa- 
sionally also in the organs. It is an infrequent type, and 
does not possess biological qualities differing from the 
large spindle-cell or polyhedral-cell sarcoma to which it is 
related.^ 

Lymphoblastoma (Synonyms: Lymphosarcoma; Lympho- 
cytoma; Malignant Lymphoma) 

These are tumors which are composed of lympho- 
blasts, and, therefore, may arise in the lymphoid tissue 
anywhere in the body. The lymphoblasts are larger than 
the lymphocytes, but may be transformed into them, con- 
sequently the tumors may contain a predominance of either 
variety of cell. The germinal centers of the nodes and 
other structures rapidly disappear as the tumor cells grow, 
so that finally the whole is replaced by lymphoblasts. 

^Prinzing: Frankfurt. Ztschr. f. Path., 1913, xiii, 289. 

101 



Eosinophile cells are occasionally present in small num- 
bers. These tumors possess no stroma of their own, the 
tumor cells simply lying free in the pre-existing connective 
tissue of the part in which they have their origin, or to 
which they have metastasized.^ 

The lymphoblastomata are prone to appear in one or 
all of three sites, the lateral aspect of the neck, coming 
from the tonsils or cervical lymph-nodes, the mediastinum, 
and the lymphoid tissue of the alimentary canal.^ Some 
thymus tumors resemble the lymphoblastomata and may 
be classed with them; others have an entirely different 
morphology, as would be expected from the histogenetic 
origin of the cells.^ 

Macroscopically, these tumors are often soft, some- 
times almost diffluent, though a hard variety is occasionally 
seen containing an excess of fibrous tissue. They are 
pinkish or greyish white on the cut surface, more opaque 
than normal nodes, and very even in consistency. They 
form lobulated masses composed of the individual nodes in 
which the tumor has arisen, but the boundaries of the dis- 
crete tumors are quickly lost by invasion of the lymphoid 
structure. They grow through the tissue which they touch 
and metastasize into the nodes and tissues with extreme 
rapidity. Almost no variety of tumor metastasizes with 
such freedom as the lymphoblastomata. Especial exempli- 
fication of this can be seen in involvement of the peritoneal 
cavity and organs. The wall of the stomach or intestine 
may be converted into a rigid tube, the fat of the omentum 
or the appendix epiploica distended with tumor cells, the 
liver diffusely infiltrated with lymphocytes.* Metastatic 

iSeelig: Surg., Gynec. and Obst., 1907, iv, 319 (bibl.) 

^Graves, S.: Jour. Med. Research, 1919, N. S., xxxv, 415 (report of 
three cases of primary lymphoblastoma of intestine, with complete 
bibl.). 

^Pappenheimer: Jour. Med. Research, 1910, N. S. xvii, 1. 

^Fabian: Zieglers Beitr., 1912, liii, 491. Infiltrating leukemia and 
lymphosarcoma. 

102 



invasion of other nodes occurs, but is at times difficult to 
establish in the gross unless anthracotic pigment has been 
deposited anterior to the entrance of the tumor cells. Such 
a deposit, however, shows that a node has been invaded, 
not that a new tumor has been formed. 

The lymphoblastomata are especially liable to have a 
multiple origin, a large number of lymph-nodes in various 
portions of the body enlarging simultaneously. This 
peculiarity is shared with another disease which is closely 
related to lymphosarcoma, that is, acute lymphatic leuke* 
mia, in which not only the bone marrow, but the organs of 
the body may be filled with tumors of lymphoid cells. The 
only distinction which can be made in many instances is 
that in the leukemias the blood contains a large number 
of lymphocytes, while in the lymphoblastomata such 
changes are very rare. 

Microscopically, the lymphoblastomata are richly cellu- 
lar tumors, the cells being larger as regards both nucleus 
and cytoplasm than the adult lymphocytes of the nodes and 
circulating blood. A certain proportion of the tumors, 
however, contain a majority of small cells with their char- 
acteristic deeply staining nuclei. Eosinophile cells may 
occasionally be present in considerable numbers. The 
stroma varies with the organs involved, being derived 
from it. 

In the soft, rapidly growing forms the connective tis- 
sue may be difficult to demonstrate except with special 
stains, but in the hard type of lymphoblastoma it occupies 
even a predominant portion of the structure, the lymphoid 
cells being contained in small alveoli. This is merely a 
growth of the trabecular supporting tissue and has nothing 
to do with the tumor proper, any more than the connective 
tissue in a carcinoma is of any but secondary importance. 

The clinical course of the lymphoblastomata is always 

103 



malignant. Cases of recovery which have been reported 
are usually based upon a faulty diagnosis. Excision of the 
primary nodule is so often followed by prompt recurrence 
in the same area, or the appearance of fresh tumors in 
other portions of the body that many surgeons now prefer 
to treat these neoplasms with Roentgen rays or radium 
rather than by excision; and some excellent results have 
followed this course. The very soft types with tendency to 
necrosis are apt to be more rapidly fatal, while the type 
with excessive fibrotic changes runs a more chronic, but 
none the less inevitably fatal, course. Occasionally cases 
are seen in which a very small primary tumor, for example, 
of the tonsil, is followed after excision, at a considerable 
interval, in one case some two years, by a large mediastinal 
metastatic growth. 

In the earlier stages this group of tumors resembles 
similar closely related types, so that the differential diag- 
nosis is sometimes impossible and in many instances very 
difficult. The conditions which must be considered are pri- 
mary or secondary carcinosis or sarcomatosis of the nodes 
affected, Hodgkin's disease, tuberculosis, syphilis, and 
other types of chronic adenitis, simple lymphomata, and 
lymphatic leukemia. 

The diagnosis of secondary carcinoma can be made by 
a glance through the microscope at a suitable section. 
Sometimes it is possible to make such a diagnosis by mere 
gross inspection of the node; but the writer has seen 
several cases in which nodes with central softening simu- 
lated either tuberculosis or lymphocytoma, which proved 
on microscopical examination to be necrotic carcinomata. 
This was true in one case of carcinoma of the larynx which 
had been excised some years previously without local re- 
currence and in another case of very small tumor of the 
breast with metastases in the axillary nodes, in which the 

104 



breast tissue itself gave no evidence of new growth on 
microscopical examination, though the nodes were enlarged 
and some of them were softened in the center. The simple 
lymphomata are at times difficult to differentiate. In them 
a lymph-node may lose all of its normal structures, and 
there may be also a moderate invasion of the capsule, and 
yet the tumor may remain free and well delimited, and 
never show malignant qualities. Occasionally it is impos- 
sible to determine microscopically whether the node is the 
site of a lymphoblastoma or of a simple lymphoma. Usually 
in the lymphoblastoma the invasion of the capsule is much 
more extensive and the neighboring nodes are rapidly in- 
volved in a large diffuse mass. This does not occur with a 
lymphoma. 

From primary sarcoma the differential diagnosis is not 
always easy without a microscopical examination. The 
multiple appearance is much more frequent in the lympho- 
cytomata than in the true sarcomata. Ulceration and 
necrosis are more frequent in the lymphocytomata, 
especially those involving the lymphoid tissue of the throat, 
than in the sarcomata. Primary sarcomata of the lymph- 
nodes are very rare. Fibrosarcomata and spindle-cell sar- 
comata of the lymph-nodes have been seen, but a micro- 
scopical examination is needed to separate them from the 
lymphocytomata. The alveolar large-cell type of sarcoma 
also occurs in the lymph-nodes, but is easily distinguished 
microscopically. 

Tuberculous adenitis, also, often requires microsco- 
pical differentiation, but if tubercles containing typical 
Langhans' giant cells are found the diagnosis is easy. The 
nodes of Hodgkin^s disease usually contain considerable 

105 



fibrous tissue and multinucleated cells, not of the Lang- 
hans' type. The extensive necroses of tuberculosis are ab- 
sent unless the nodes are also at the same time involved 
by a true tuberculous lesion. 

Syphilitic lymph-nodes in most cases show merely a 
hyperplasia of the lymphoid tissue with swelling of the 
endothelial cells of the sinuses and reticulum; gummata 
are extremely rare. If the case has not been recently 
treated, a positive Wassermann reaction will be of value, 
though it must be remembered that lymphoblastomata may 
occur in persons who have previously suffered from syphilis. 
The therapeutic test is useful, but should not be continued 
if the nodes resist treatment with arsphenamin or mercury 
plus potassium iodide. 

The differentiation of the leukemic nodes rests chiefly 
upon the examination of the blood. Occasionally the diag- 
nosis is difficult because the true tumors may be accom- 
panied by extreme leucocytosis, and the blood in some cases 
of lymphatic leukemia may contain but few cells. The ab- 
sence of myelocytes from the blood and the relatively low 
percentage of the lymphocytes with increased eosinophiles 
usually point towards lymphocytoma. The spleen and liver 
are not so extensively enlarged as is usually the case in 
leukemia; and the leukemic nodes are apt to remain dis- 
crete and movable for a long period. 

The presence of a lymphoblastoma may incite a lymph- 
adenitis in the neighboring nodes so that care must be 
taken to avoid an incorrect diagnosis where a single node 
has been excised for examination. Very frequently such a 
node may show only slight inflammatory lesions and unless 
the history of the case is known to the pathologist an 
erroneous diagnosis of simple adenitis may be made. It is 
necessary, therefore, to obtain one of the nodes involved 

106 



by the tumor rather than to excise for diagnosis a small 
easily movable neighboring superficial nodule which fre- 
quently does not show the characteristic changes. 

Plasmocytoma 

This tumor is composed of plasma cells, and is closely 
related to the lymphoblastomata, but differs from them in 
being benign. The diffuse types arising from the bone 
marrow may, however, be malignant, forming one class of 
the myelomata. The tumors are rare, and only a few have 
been described.^ Among the cases reported, those of the 
clearest neoplastic relations are a growth of the size of a 
walnut from the palate,^ one from the tongue,^ and one 
from the pleura.* Other tumors attributed to this class 
have a morphology suggesting inflammatory rather than 
neoplastic qualities.^ 



Myeloma 

The myelomata form a peculiar group of tumors which 
are derived from the cells of the bone marrow, and in some 
respects resemble the sarcomata, though differing from 
them in histogenesis.^ The tumors are usually multiple, 
appearing simultaneously in many bones as reddish or 
grayish masses, are generally limited to the skeletal 

iBoit: Frankfurt. Ztschr. f. Path., 1907, 1, 172. Frank: Verhandl. d. 
deutsch. path. Gesellsch., 1913, xvi, 115. Zimmermann: Virchows Arch, 
f. path. Anat., 1914, ccxvi, 214. 

^Werdt: Frankfurt. Ztschr. f. Path., 1911, vi, 180. 

3Jessup: Proc. New York Path. Soc, 1912, xii, 6. 

*Klose: Beitr. f. klin. Chir., 1911, Ixxiv, 2-0. 

^Vogt, E.: Frankfurt. Ztschr. f. Path., 1912, x, 129 (bibl.) ; Rogers, 
J. T.: Canad. Med. Assn. Jour., 1920, x, 223. 

^Vance, B. M.: Am. Jour. Med. Sc, 1916, clii, 693 (bibl.); Christian, 
H. A.: Jour. Exper. Med., 1907, ix, 325. 

107 



system, and are possibly due to a general affection of the 
bone marrow, since the assumption that widespread mul- 
tiple growths are due only to transportation is unjustified 
by the facts. The ribs and sternum are the most frequent 
sites, the vertebrae, skull, femur, pelvis, and humerus, in 
the order named, being less frequently involved. The 
ilium was the primary seat in three of the reported cases. ^ 
In one instance, twenty-eight separate tumors were ob- 
served in the skull.^ In their growth the tumors infiltrate 
and destroy the bone and replace the marrow, so that 
spontaneous fractures are frequent, and bending of the 
bone from deficiency of lime salts may occur. Extensive 
deformity of the skeleton may be marked in the later 
stages.^ Metastases in other organs are rare,* but have 
been seen in the tonsil, liver and spleen, lymph-nodes, 
adrenals, and ovaries,^ while in cases of extremely malig- 
nant type almost every organ in the body may be involved. 

The growths vary in size from a bean to an orange, 
and may be soft or firm, translucent or opaque. The color 
also varies depending upon the amount of the blood supply. 

In all types of myelomata there appears in the urine 
a peculiar albumose, called the Bence-Jones' protein, the 
mode of formation of which is not yet determined. It is 
not diagnostic of myeloma, however, as it may occur in 
some of the leukemias, and has been reported in cases of 
chloroma, myxedema, chondrosarcoma, and osteomalacia. 

Multiple myeloma is a disease of middle life, occurring 
chiefly in males between the ages of twenty-five and 
seventy. An infectious origin has been suggested because 

iHoffmann, A.: Zieg-lers Beitr., 1904, xxxv, 317. 

^Winkler: Virchows Arch., 1900, clxi, 252. 

^Foi? an interesting- anatomical study, see Meyer, A. W., and Swain, 
R. E.: Am. Jour. Med. Sc, 1918, clvi, 329. 

^Symmers, D.: Ann. Surg-., 1918, Ixvii, 687. 

^Pepper, O. H. P., and Pearce, R. M.: Jour, Med. Research, 1918, N. 
S. xxxii, 171; Norris, C: Proc. New York Path. See, 1906, vi, 128. 

108 



of the clinical features and the relatively slow course, and 
in some cases the growths have been referred to trauma, 
though without sufficient evidence. 

Microscopically, the tumors are composed of five 
varieties of cells: myelocytes with neutrophile granules, 
myeloblasts, lymphocytes, nucleated red cells, and plasma 
cells. The most frequent type is that composed of plasma 
cells, which may be large or small, with single or multiple 
nuclei. In the tumors formed chiefly of myelocytes (myelo- 
cytoma) the cells are large, with oval or irregular nuclei, 
many of them showing characteristic granulations and giv- 
ing the oxidase reaction. Giant cells may be present. The 
tumors consisting mainly of red cells (erythrocytoma or 
erythroblastoma) are rare. In a recently reported case 
bone marrow plasma cells were found in the circulating 
blood.^ 

Chloroma 

Chloroma is the name applied to a disease in which 
greenish tumors appear chiefly in the bones. ^ It is closely 
related in many aspects to the leukemias. The disease is a 
rare one, less than one hundred cases having been reported, 
and occurs most often in young males, running an acute 
course and terminating fatally. The tumors appear chiefly 

iBeck, H. G., and McCleary, S.: Jour. Am. Med. Assn., 1919, Ixxii, 480. 

2Dock: Am. Jour. Med. Sc, 1893, cvi, 162; Dock and Warthin: Med, 
News, 1904, cv, 971; Sternberg-: Lubarsch-Ostertag-, Erg-ebn. d. allg. 
Path., 1903, ix^, 360 (very important paper giving the author's opinions 
on the primary diseases of the blood-forming organs and the lymphatic 
system) ; Lehndorff : Ergebn. der inn. Med., 1910, vi, 221 (a very com- 
plete discussion of all published cases to date and a copious biblio- 
g-raphy) ; Burgess: Jour. Med. Research, 1912, N. S. xxii, 133 (bibl.) ; 
Walls and Goldsmith: Am. Jour. Med. Sc, 1914, cxlvii, 836 (complete 
bibl.); Boots: Jour. Lab. and Clin. Med., 1916-17, ii, 622 (bibl.). 

109 



in the skull, involving the orbit, the auditory region, causing 
deafness, the sinuses, and the nasopharyngeal cavities. In 
many instances, other bones of the body are also involved. 
The lymph-nodes are usually affected and the bone marrow 
contains the greenish tumor material. The spleen is also 
involved, and the liver and kidney may show deposits. The 
blood may be normal, except for a marked anemia. In 
other instances, the picture is that of an acute lymphatic 
leukemia, or a myelocytic leukemia. The lymphocytic type 
is most frequently seen. The number of cells varies greatly, 
as high as 500,000 to the cubic millimeter having been 
found. The tumors usually appear as flat thickenings, 
fairly firm, involving the bony structure. There is generally 
some resorption of the bone, with rarefaction of the trabe- 
culae. On cross section the tumors are fairly consistent in 
structure, usually greenish, though the tissues may be mot- 
tled green and white, and in some instances most of the 
tumor may be white rather than green. 

Microscopically, the tumors are composed of either 
lymphocytes or lymphoblasts, or of myeloblasts. In the 
latter case, the oxidase reaction is given by the cells. Noth- 
ing definite is known as to the chemical nature of the 
pigment; but a similar color has been observed in the bone 
marrow of cases of acute lymphatic leukemia. Bence-Jones' 
albumose has been found in the urine of cases of chloroma 
of the myelocytic type. 

Differentiation from leukemia or lymphosarcoma is 
impossible unless the fragments of tumor can be examined 
and the green color noted. Many of the myelogenous types 
have been considered as myelogenous leukemias and shown 
to be chloroma only on autopsy. 

110 



Leukemia 

While not by any means generally accepted, the view 
is held by many pathologists of ability^ that the leukemias 
are neoplasms of the bone marrow cells or of the lymphoid 
tissues and belong in the class of tumors. According to 
this theory the appearance of the cells in the blood is merely 
an accidental occurrence depending on the topography of 
the growth, which by invasion of the capillaries permits 
the entrance to the blood-current of the cells of the tumor, 
and adherents of this view point out that in some instances 
of lymphoblastoma large numbers of cells may appear in 
the circulating blood. In acute lymphatic leukemia (Stern- 
berg's leucosarcomatosis), also, metastatic deposits in the 
skin are frequently, but not always, found, as well as ex- 
tensive involvement of the lymph-nodes throughout the 
body, including the splenic tissues. In myelogenous leuke- 
mia, the spleen growth is assumed by the adherents of the 
tumor theory to be a metastatic deposit from the bone 
marrow, but in the chronic types of this disease skin metas- 
tases do not occur. In many instances, metastatic growths 
appear in the liver and kidney. This is especially true of 
the lymphatic leukemias. The growth in the bone marrow 
may give rise to such resorption of bone tissue as to result 
in spontaneous fracture. In some instances metastatic 
formation of tumor-like nodules has been so extensive in 
the organs, for instance, the breast, as to lead to a clinical 
diagnosis of lymphosarcoma. ^ In such tumor-like nodules, 

^The following are references to the work of those who believe in 
the tumor theory: Mallory: Principles of Pathologic Histolog-y, Phila- 
delphia, 1914, p. 326; Ribbert: Geschwulstlehre, 2d ed., Bonn, 1914; 
Banti: Centralbl. f. path. Anat., 1904, xv, 1 (leukemia); Burgess: Jour. 
Med. Research, 1912, N. S., xxii, 133 (chloroma) ; Roman: Zieglers Beitr., 
1912, lii, 385 (malignant myelomata) ; ibid., 1913, Iv, 61 (myeloid chloro- 
leukemia) ; Fabian, Naegeli, and Schatiloff: Virchows Arch. f. path. 
Anat., 1907, cxc, 436; Fabian: Zieglers Beitr. 1912, liii, 491 (leukemia 
and lymphosarcoma); v. Domarus: Folia haemat., Archiv, 1912, xiii, 384. 

2McWilliams and Hanes: Am. Jour. Med. Sc, 1912, cxliii, 518. 

Ill 



the cells of the organ in which the deposit occurs are 
pressed aside and to a certain extent destroyed by the 
enormous growth of the specific tumor cells. Invasion 
of the omentum sometimes occurs, so that the condition 
resembles those infiltrations seen in the lymphoblastomata. 

On the other hand, the prevalent opinion is that the 
leukemias are diseases of unknown origin, in many in- 
stances infections giving rise to hyperplasias of the 
lymphoid and myeloid tissues wherever these may occur in 
the body. This is especially true of the acute lymphatic 
and myelogenous types. In the chronic myelogenous form 
the disease seems to be confined to the spleen during the 
earlier part of the disease. 

Organisms have been demonstrated in a certain num- 
ber of the acute lymphatic cases, but no causal relationship 
to the disease has yet been shown. A picture very closely 
simulating acute lymphatic leukemia is often seen, how- 
ever, in severe Vincent's angina, and the only means of 
differentiating the two conditions is observation of the case. 
In Vincent's angina the blood returns to normal a week or 
two after the acute inflammatory process has subsided, 
whereas in the leukemias the disease is always progressive 
and fatal. 

The remarkable improvement in the leukemic condition 
of the blood and in the general health following radiation 
of the spleen in certain cases of myelogenous leukemia has 
been used by adherents of both theories as confirming the 
tumor-like nature or as disproving it. The fact remains 
that many persons suffering from this disease may be kept 
alive for a period of from two to five years, the blood being 
practically normal, though occasional myelocytes are found. 
The chronic lymphatic leukemias temporarily yield to 
radiation, but not as obviously as do the myelogenous, 
while the acute types are very little helped by exposure to 
either radium or x-ray. 

112 



TUMORS OF MUSCLE TISSUE 

MYOMA 

Tumors containing muscle fibers are divided into two 
groups, those containing striated muscle fibers, or the 
rhabdomyomata, and those containing unstriated muscle 
fibers, or the leiomyomata. 

Rhabdomyoma 

Pure rhabdomyomata are very rarely found. The 
more frequently occurring variety contains, in addition to 
the striated muscle fibers, connective tissue of various 
types, cartilage, and epithelial islands or cysts. Such 
tumors might properly be grouped, therefore, among the 
teratomata. Even including this class, the total number of 
rhabdomyomata described is probably less than one hun- 
dred. 

Macroscopically, these tumors do not resemble very 
closely muscle tissues, even in the pure types. They are 
usually either paler, softer, or harder than the normal 
muscle tissue, and this difference is due to the fact that 
usually more connective tissue is present in the mass than 
in normal muscle, and also that the muscle fibers of the 
tumor are not completely developed. 

Microscopically, the muscle fibers are almost never of 
the normal type, but resemble the imperfectly developed 
forms seen in the embryo. They are, therefore, usually 
spindle shaped, or may assume oval or round forms. 
Branched and giant cells are also occasionally seen. The 
relation of the individual muscle fibrils is often irregular, 
and single strands may surround the nucleus in concentric 
bundles. Often the longer fibers are so narrow that they 

113 



resemble connective tissue cells, but usually the transverse 
striations can be made out in some portion of the muscle 
fiber, though it may be necessary to employ the higher 
powers of the microscope. Transverse sections of the 
muscle often show a canal-like lumen with the nucleus lying 
in the center. A well developed sarcolemma is usually ab- 
sent, though some trace of the structure may occasionally 
be seen. Particles of glycogen may be very frequently 
demonstrated in the muscle fibers by suitable stains, 
especially in those fibers which assume a round or club- 
shaped form. The presence of this material in such form 
is an indication of the embryonal character of the muscle 
element. All these facts point to the origin of a tumor in 
displaced areas of muscle tissue, which in the earlier part 
of embryonic life have become separated from their nor- 
mal situation. The rare "homologous'' type of rhabdo- 
myoma, which occurs where muscle tissue is normally found 
and contains but little else, is seen in the walls of the heart 
and is associated with other congenital malformations, 
such as adenoma sebaceum, complex kidney tumors, and 
tuberous cerebral sclerosis.^ Homologous rhabdomyoma 
may occur elsewhere in the voluntary muscles of the body, 
but with the greatest rarity.^ 

The ''heterologous" rhabdomyomata, which are much 
more frequent than the previous form, originate at sites 
where no striated muscle occurs normally, and form gen- 
erally a portion only of a complex tumor. The most fre- 
quent place for this type of rhabdomyoma is the kidney. 

iDelafield and Prudden: Text Book of Pathology, New York, 1919, 
11th ed., p. 1114; Wolbach: Jour. Med. Research, 1907, N. S., xi, 495; 
Abricossoff: Zieglers Beitr., 1909, xlv, 376 (bibl.); Bundschuh: Zieglers 
Beitr., 1912, liv, 278; Rehder: Virchows Arch. f. path. Anat., 1914, cxxii, 
174; Ribbert: Centralbl. f. allg-. Path. u. path. Anat., 1915, xxvi, 241. 
Kawamura: Centralbl. f. allg. Path. u. path. Anat., 1913, xxiv, 301; 
Neurath: Lubarsch-Ostertag, Ergebn. d. allg. Path., 1908, xii, 732 (bibl.). 
For details of the kidney tumors occurring with tuberous cerebral 
sclerosis, see Kirpicnik: Virchows Arch. f. path. Anat., 1910, cii, 358. 

2Kuttner, H., and Landois, F., Deutsch. Chir., 1913, i, 25A; Fujinami: 
Virchows Arch. f. path. Anat., 1900, clx, 203. 

114 



In this organ they reach a very large size and may destroy 
practically all the kidney substance. The testicle also is 
a comparatively frequent site, and the tumors occur in the 
walls of the bladder, and in the prostate, ureter, spermatic 
cord, esophagus, and parotid.^ In the testicle the muscle 
fibers are usually scattered through a considerable mass of 
loose connective tissue, the latter containing cysts lined 
with epithelium of various types — cylindrical, ciliated, or 
squamous — in other words, elements of a teratoid tumor.^ 
The homologous rhabdomyoma are, as a rule, apt to 
be only locally malignant, but in the heterologous type, 
metastasis either of a sarcoma or carcinoma, or more rarely 
of muscle tissue has occurred in the regional nodes and 
elsewhere.^ Such metastatic recurrences have been noted 
most frequently in connection with rhabdomyoma of the 
testicle; in a few instances with muscle metastases, and 
in others with metastatic nodules of a sarcomatous nature, 
evidently derived from the interstitial tissue of the tumor.* 

Leiomyoma 
(Synonym: Myoma levicellulare) 

Tumors of this type are composed of non-striated 
muscle cells lying in closely packed bands, and separated 
from each other by a variable quantity of more or less 
vascular fibrous connective tissue. 

The pure leiomyomata, in which the amount of con- 
nective tissue stroma is very small, occur chiefly in the 
female genitourinary tract, the gastrointestinal canal, and 

^Prudden: Am. Jour. Med. Sc, 1883, Ixxxv, 438. 

^Benenati: Rhabdomyoma in a displaced testicle, Virchows Arch, 
f. path. Anat., 1903, clxxi, 418; Wood: Proc. New York Path. Soc, 1902, 
i, 52. 

^Wolfensberger: Zieglers Beitr., 1894, xv, 491 (bibl.). 
^Stoerk: Ztschr. f. Heilk., 1901, xxii, 200; Burgess: Jour. Med. Re- 
search, 1913-14, N. S., xxiv, 447. 

115 



the skin,^ and sometimes in the veins.^ These are all rare 
tumors. A more common type is the fibromyomata, which 
are not infrequent in the walls of the gastrointestinal tract, 
and in the bladder, prostate, vagina, and kidney, and are 
most often seen in the uterus.^ These last are among the 
most frequently encountered of all tumors, occurring in 
almost 20 per cent, of all women over thirty-five years of 
age. In the uterus, they are often multiple, and may be 
found in various sizes in the same organ, from small 
growths composed almost entirely of muscle fibers and 
measuring only a few millimeters in diameter, up to 
enormous masses which may weigh 50 kilograms, and fill 
almost the entire abdominal cavity. Most of the myomata 
are situated in the wall of the uterus (interstitial myo- 
mata), but they may occur also in the subserous and sub- 
mucous layer, and may even form hard or soft polypoid 
growths containing only muscle and fibrous tissue, or a 
few glands of the endometrium. 

In the later stages of development of a myoma, when 
the tumor has reached a large size, it is sometimes difficult 
to determine whether the growth has started in the mus- 
culature of the wall or has pushed its way outward so as 
to become subserous, or inward, so as to become sub- 
mucous. In other instances, the myoma may grow laterally 
into the broad ligament, but usually if a myoma has begun 
in the wall of the uterus and ultimately become submucous 
by growth inward, it is possible to demonstrate a cap of 
uterine musculature on its projecting surface, in contrast 
to the growth which has been submucous or subserous from 

iLieber: Zieglers Beitr., 1915, Ix, 449 (bibl.). 

^Schneider: Gentralbl. f. allg-. Path., 1914, xxv, 529. 

^Por details concerning myomata of the uterus, see Kelly and 
Cullen: Myomata of the Uterus, Philadelphia, 1909; Lockyer: Fibroids 
and Allied Tumors, London, 1918; Eden and Lockyer: The New System 
of Gynaecolog-y, London, 1917, ii, 191; Meyer, R.: Veit, Handb. d. 
Gynakologie, 2d ed., Wiesbaden, 1907, i, 415. 

116 



the beginning. The subserous myomata may extend out- 
ward and ultimately possess only a narrow pedicle so that 
they hang free in the peritoneal cavity and finally, 
either by torsion of the pedicle or by traction on the same, 
separate themselves from the uterus and form free masses 
in the pelvis where they may undergo degeneration and 
calcification. The interstitial myomata are the most com- 
mon, forming about three-quarters of all those found; the 
submucous form about 15 per cent.; and the subserous ap- 
proximately the 10 per cent, remaining. Myomata are 
usually derived from the body of the uterus, but a small 
percentage, perhaps about 5 per cent, on the average, arise 
in the cervix. The walls of a myomatous uterus are almost 
always thickened, probably due to functional hypertrophy 
following excessive muscular contraction of the uterus in- 
cited by the irritation of the presence of the tumor. Fibro- 
myomata of the uterus are usually slow growing tumors, 
but the rate depends on the degree of vascularization and 
other general conditions, such as frequency of menstrua- 
tion or of pregnancy. After the menopause, they cease to 
grow unless nourished by peritoneal adhesions and in many 
instances diminish in size or wholly disappear. If the 
menopause is artificially induced by the action of radium 
or Roentgen rays, the same atrophy is observed. A rapid 
increase in the growth rate hints at the presence of sar- 
comatous changes or alterations in the circulation, produc- 
ing edema or hemorrhage. 

Macroscopically, the fibromyomata are hard, if fibrous, 
and soft, if muscular tumors. They are generally spherical 
or ovoidal, but the entire uterus may be altered into a myo- 
matous mass and still retain its normal form. The surface 
of the section due to the interlacing bundles of connective 
tissue and muscle fibers has a watered silk appearance. If 
the amount of connective tissue is small the tumor is apt 
to be of a reddish color, if the fibrous tissue predominates, 

117 



of a lighter tone, reaching a pure white. Deep red tumors 
usually show degenerative changes or hemorrhage. At the 
periphery of the tumor is a capsule of stretched-out uterine 
muscle, and in this capsule the larger blood-vessels and 
lymph-channels run. In som^ instances, especially in the 
cervix myomata, the capsule is so perfect that the tumor 
can easily be shelled out of the substance of the uterus. 
The uterine cavity is frequently so distorted that it is 
difficult to demonstrate it. The tumor, if of any size, 
presses forward the mucous membrane and flattens it, and 
only those portions which are not in direct contact with the 
tumor show hyperplasia, with high cylindrical epithelium 
lining the endomietrial glands. Carcinoma is not infre- 
quent in myomatous uteri; and secondary changes in the 
myomata are extremely common. With age, the fibrous 
tissue increases and the muscle fibers atrophy, so that 
ultimately very few are present. Exceptionally, however, 
newly formed, richly cellular, small myomata may be found 
after the menopause. Hyaline degeneration of the dense 
connective tissue is very often found; hemorrhages are 
not infrequent; edema is extremely common; mucoid or 
fatty degeneration is occasionally seen; calcification and, 
in rare instances, bone formation may occur following de- 
generative necrosis, due to some interference with the cir- 
culation. Infection, with subsequent inflammation or even 
gangrene of the tumor, may occur. Tuberculosis is very 
rare. 

Microscopically, the fibromyomata show little of in- 
terest; interlacing bundles of muscle fibers with their long 
narrow nuclei and fairly well marked cell bodies mingled 
with more or less fibrous tissue form the regular picture. 
The muscle cells are usually larger than those normal to 
the uterine musculature, and the nuclei share this increase ; 
the cell body is strongly acidophilic, taking a deep stain 
with eosin. Mitoses are almost never found. 

118 



When the myomatous tissue becomes edematous, the 
muscle fibers may be separated from the rest of the tissue 
in small bundles in which the individual cells are easily 
made out. In the firmer varieties, muscle tissues are some- 
times difficult to find, but usually in some portion of the 
growth areas will be present formed almost wholly of 
muscle fibers, and unless care is used in examining a prepa- 
ration a beginning sarcoma may be suspected, though with 
a reasonably careful study of the situation this danger can 
be eliminated. In rare instances, the vascular supply may 
be so great that the tumor presents the appearance of an 
angioma or angiosarcoma. Usually, however, the vessels 
are thick-walled and not very abundant. Thrombi may be 
found when the circulation has been interfered with by 
edema. If this is extensive, the center of the tumor may 
be softened, and a cyst may be formed in the substance 
of the myoma, in which secondary changes occur. If no 
infection or hemorrhage has taken place in the contents of 
the cyst this may be filled only with edema fluid or lymph. 
If, on the other hand, infection has taken place the wall 
may be thickened and calcified deposits may be formed. If 
no infection has occurred but some hemorrhage has taken 
place, cholesterin crystals are frequent in the dark con- 
tents of the cyst. 

In the vast majority of instances the fibromyomata 
are benign, but occasionally rapidly growing metastasizing 
tumors of this type have been found in the uterus; these 
will be considered under the muscle sarcomata. The diag- 
nosis of a simple fibromyoma is extremely easy, and rarely 
requires a microscope. When the tumor is from an unusual 
site and must be differentiated from a fibroma or sarcoma 
the following details may be of value. The body of the 
muscle cell is usually fairly sharply outlined and the long 
rod-shaped nucleus with rounded ends is different from 
that of the connective tissue cells, which is spindle-shaped 

119 



and relatively shorter. Cross sections of the muscle cells 
usually show that the nucleus lies inside the cell in an area 
which is apt to be clear, owing to the shrinkage of the 
cytoplasm from the nucleus. Cross sections of connective- 
tissue cells show the nucleus lying on one side of the cell 
body if the latter is visible. Another differential point is 
that the non-striated muscle ends in a rounded conical 
point which can usually be seen with the high powers of 
the microscope, while the fibrous tissue cells break up into 
wavy bundles of collagen fibers. To demonstrate these 
facts the tissue should be very promptly fixed in Zenker's 
fluid and stained by special methods, many of which we 
owe to the painstaking studies of Mallory.^ At times it is 
absolutely necessary to use special stains, the most im- 
portant of which are Van Gieson's, in which the picro-acid 
fuchsin colors the muscle yellow and the connective tissue 
red, Weigert's iron hematoxylin picro-acid fuchsin which 
has the same action, and Mallory's aniline-blue-orange-G 
mixture, which colors the muscle red and the connective 
tissue blue. But these stains are rarely necessary except 
in some of the unusual leiomyomata, such as occur in the 
neck about the muscles and are derived from the striated 
muscles of the wall, or in unexpected places. 

The differential diagnosis of fibromyoma from sar- 
coma is often possible in the gross. The sarcomata are 
softer; they do not show the interlacing bundles of fibrous 
tissue, but are opaque, putty-like, and relatively structure- 
less on cross section. They are much more liable to have 
softer areas; they are usually discrete in the wall of the 
uterus and do not fuse into it, though, of course, in some 
instances, the entire uterus may be converted into a mass 
of sarcoma. The malignant change may be entirely con- 
fined to a pedunculated growth, which hangs in the cavity 

^Mallory: Jour. Med. Research, 1904-05, N. S., viii, 113. 

120 



of the uterus, and none of the rest of the wall show any 
changes. Small, very cellular areas occur in many myo- 
mata and by some are considered a sarcoma, by others 
not. This has led to a wide difference of opinion as to the 
frequency of the presence of sarcoma in the uterine myo- 
mata, certain pathologists stating that even 10 per cent, of 
all uterine myomata contain sarcomata,^ though 1 per cent, 
is probably nearer the facts. One very misleading point 
is the fact that the sarcomata may be well encapsulated, 
even though on microscopic examination the invasion of the 
musculature may be apparent. If the sarcoma of the uterus 
remains confined to the muscular tissue or in the center of 
a fibromyoma it may show no clinical evidence of malig- 
nancy for a long time, and many of the cases after hyste- 
rectomy never show evidences of recurrence. 

Adenomyoma 

A special form of myoma is the adenomyoma often 
seen in the uterus and very rarely in the round ligament, 
the rectovaginal septum, and the umbilicus.^ The peculiar- 
ity of this type is that glandular structures are present in 
the tissue. In the uterus, they occur in all portions, though 
most frequently on the posterior surface, while small col- 
lections of glands hardly to be designated as tumors often 
occur at the tubal angle, as was originally shown by von 
Recklinghausen.^ Occasionally the entire uterus may be 
changed into an adenomyomatous mass. The most fre- 

iCullen: Jour. Am. Med. Assn., 1906, xlvi, 695; Evans: Surg., Gynec, 
and Obst., 1920, xxx, 225 (bibl.) 

^Cullen: Adenomyoma of the recto-vaginal septum, Bull. Johns 
Hopkins Hosp., 1917, xxviii, 343; Cullen: Adenomyoma of the Uterus, 
Philadelphia, 1908; Cullen: The Umbilicus and its Diseases, Philadelphia, 
1916; Mahle, A. E., and MacCarthy, W. C: Ectopic adenomyoma of uterine 
type: Jour. Lab. and Clin. Med., 1920, v, 218. 

^von Recklinghausen: Die Adenomyome und Cystadenome des 
Uterus, Berlin. 1896. 

121 



quently occurring lesion is a small area of endometrium 
containing one or two endometrial glands, either normal or 
dilated, lying almost anywhere deep in the wall of the 
uterus and surrounded by myomatous tissue. These ade- 
nomyomata can be found on careful microscopical search in 
a considerable proportion of uteri, and Cullen has shown 
that unquestionably such structures are produced during 
the formation of the uterus by displacement of fragments 
of the endometrium itself. On the other hand, some of 
these nodules are so distant from the mucous membrane 
or so entirely separated from it, that the assumption is 
justified that they are derived from some embryonal ab- 
normality associated with the development of the Wolffian 
duct or even Miiller's duct. Some of them probably arise 
from epithelial downgrowths from the endometrium into 
fistulous channels in the musculature of the uterus after 
abscesses of the wall. The subserous adenomyomata are 
probably formed of peritoneal epithelium. 

The adenomyomata are but of little clinical importance, 
except that occasionally carcinoma has been observed to 
arise in them, or the glands may become greatly dilated 
and give rise to the formation of a cyst of considerable 
size. Inflammatory processes, also, may appear in the gland 
tubules, and menstrual and decidual changes occur coinci- 
dent with similar processes in the endometrium. The 
adenomyomatous masses rarely have a well defined capsule, 
and, therefore, cannot be shelled out as can the fibromyo- 
mata. 

The diagnosis is usually easy. Occasionally the glands 
are so large that the adenomyomatous area of uterus may 
be recognized in the gross. Microscopically, they are lined 
with a high cylindrical, sometimes ciliated, epithelium and 
resemble perfectly the glands of the endometrium, but in 
order to justify a diagnosis of adenomyoma they must be 
surrounded by a remnant of endometrium. 

122 



Myosarcoma (Malignant Myoma) 

Myosarcomata are tumors composed essentially of 
muscle cells. The nomenclature of the malignant tumors 
arising in myomatous tissue is somewhat confused. The 
following classification has been suggested:^ 

1. Malignant myomata. Neoplasms in which the 
primary growth and the metastases both show structures 
corresponding to normal fibromyomata, so that the only 
evidence of malignancy is the ability to metastasize. 

2. Myosarcomata. Sarcomata arising from the in- 
termuscular connective tissue, and not differing from sar- 
comata elsewhere except that muscle fibers may be included 
in the primary growth. 

3. Myoblastic sarcomata. Heterotypical tumors of 
regions where smooth muscle cells are present, arising from 
undifferentiated embryonal muscle cells. 

4. Myogenic sarcomata. Tumors beginning in fully 
developed muscle cells. These tumors are closely related to 
the malignant myomata included under heading 1. 

Myomata which metastasize occur chiefly in the gas- 
trointestinal tract and the uterus. A few cases have been 
reported in which the myoma metastasized to a distance, 
though retaining the morphology of the primary growth 
and showing no definite evidence of a contamination with 
sarcoma.- The structure of these metastasizing myomata 
is not very different from that of the original growth from 
which they spring ; and the metastases consist of a mixture 
of smooth muscle fibers and connective tissue. The tumors 
are, however, extremely rare. 

iHoevels: Frankfurt. Ztschr. f. Path., 1911, viii, 477. 

^Moser: Ueber myosarkom des Magens, Deutsch. med. Wchnschr., 
1903, xxix, 133, 157; Eising, E. H.: Two cases of myoma sarcomatodes. 
Jour. Path, and Bacteriol., 1903, viii, 233 (bibl.); Ghon, A., and Hintz, 
A.: Ueber maligne Leiomyoma des Intestinaltraktes. Zieglers Beitr., 
1909, xlv, 89 (bibl.); Hoevels, K.: Ein Fall von myoblastischen Sarkom 
des Uterus mit Lungen-und Nierenmetastasen, Frankfurt. Ztschr. f. 
Path., 1911, viii, 477 (bibl.). 

123 



Another type from which they must be distinguished 
is that of a pure spindle-cell sarcoma arising in a myoma 
or in the wall of the gastrointestinal tract. This does not 
differ from spindle-cell sarcomata elsewhere either in its 
morphology or in its clinical qualities. 

A wholly different type of tumor is the malignant 
myoma which develops in the uterus and shows marked 
morphological changes from the structures from which it 
arises. These tumors are fairly frequent, forming one to 
four per cent, of all myomata removed by operation. They 
vary greatly in their morphology from a tumor resembling 
a simple spindle-cell sarcoma ; no muscle fibers can be found 
composing the tumor itself, the nuclei being the long nar- 
row nuclei characteristic of muscle tissue. They may con- 
tain no mitotic figures and be almost indistinguishable from 
a richly cellular myoma. At the other end of the scale are 
tumors which contain very large irregular cells with nuclei 
of a large size containing chromatin in very great abun- 
dance. Some of these cells are giant in size. Various types 
of irregular mitoses are frequent. There is usually little 
stroma between the cells and the blood-vessels are very 
thin. Hemorrhages into the substance of the tumor are 
common.^ 

TUMORS OF PIGMENT CELLS 

Melanotic Tumors (Synonyms: Melanoma, Chromatopho- 

roma) 

The melanomata derive their name from their charac- 
teristic color, which is due to the brownish or yellowish pig- 
ment contained in the tumor cells. The tumors occur chiefly 

lEvans: Surg-., Gynec, and Obst., 1920, xxx, 225: Geist: Am, Jour. 
Obst., 1914, Ixix, 766; Strong: Am. Jour. Obst., 1915, Ixxi. 230; Kelly and 
Cullen: Myomata of the Uterus, Philadelphia, 1909; Proper and Simpson: 
Surg., Gynec, and Obst., 1919, xxix, 39. 

124 



on the skin^ or in the subcutaneous tissues, but are also 
found on the choroid of the eye, the iris, or the conjunc- 
tivae, on the mucous membrane of the pharynx and rectum, 
in the central nervous system,^ as primary tumors on the 
nerve trunks, and in many of the organs. 

The skin tumors frequently take their origin in con- 
genital moles, either the pigmented or the non-pigmented 
varieties, but they may be independent of any visible 
change in the skin; and possibly the importance of moles 
as potential melanomata has been somewhat exaggerated. 
The majority of people possess these congenital defects, 
which in but few cases become malignant.^ Many sur- 
geons, however, believe that the chief hope in reducing the 
mortality of this most fatal type of neoplasm must be 
placed in prophylactic treatment; that is, the prompt re- 
moval of pigmented moles in all cases in which the anatomic 
locality renders them liable to irritation or injury.^ 

No portion of the surface of the body is entirely ex- 
empt from melanomata, but they are relatively frequent on 
the plantar aspect of the feet and toes, on the upper ex- 
tremity, and, also, on the face. Usually they are covered 
with epidermis, and as they begin to grow the tumor fre- 
quently breaks through the skin and ulcerates. The cho- 
roidal tumors may remain limited to the eye for a very 
considerable time, gradually filling it with neoplastic tissue. 
Early operation gives fairly good results, local recurrence 
being unusual; but metastases at a distance, especially in 
the liver, are unfortunately frequent. The melanotic tumors 
are among the most malignant of all forms known, and not 
only involve the lymph-nodes very early, but also invade 
the blood-vessels and form metastases throughout the body, 

iWilson and Kalteyer: Am. Jour, Med. Sc, 1903, cxxvi, 751. 
^Fordyce: Jour, Am. Med. Assn., 1910, liv, 91. 
^Hirschberg-: Virchows Arch. f. path. Anat., 1906, clxxxvi, 229. 
■*Coley and Hoguet: Ann. Surg., 1916, Ixiv, 206. 

125 



enormous masses occurring especially in the liver, occa- 
sionally replacing most of the substance of the organ. An 
interesting form of metastasis is seen hanging free in the 
pleural, pericardial, or peritoneal cavities, and especially 
in the bladder, where the tumor may form long, fringed 
masses attached to the wall by a narrow pedicle merely 
and demonstrable on cytoscopic examination as waving 
about as the urine is agitated. At their inception, the skin 
tumors are usually flat or slightly raised nodules, or are 
lobulated, and are usually of a very black color, though 
occasionally they are brownish or yellowish. About the 
primary growth there are often small secondary growths 
at a few centimeters distance lying just under the epider- 
mis. Metastases may occur when the primary growth is 
very small, the pigmented mole having given so little evi- 
dence of its malignant nature that the patient applies for 
relief from symptoms due to the large deposits in the in- 
ternal organs.^ Especially is this true of the melanomata 
of the feet, because in this situation there is a continual 
massage of the tumor as the patient walks about, and 
tumor cells are transferred very early to the lymph-chan- 
nels or blood-current. Probably many of the tumors de- 
scribed as primary melanomata of the internal organs are, 
for this reason, actually metastatic deposits from some 
melanotic tumor so small that it has been overlooked. The 
melanotic neoplasms of the eye, while highly malignant, 
may, if diagnosed early, as is the rule, and promptly re- 
moved, furnish metastases only a long time after the ex- 
cision of the growth. Cases are on record in which fifteen 
to twenty-four years after such an excision the patient died 
of metastatic growths in the internal organs. The tumors 
appear chiefly in the upper age groups, between the ages 
of forty and sixty years. They are, fortunately, relatively 

iQaskill: Jour. Am. Med. Assn., 1913, Ix, 341. 

126 



rare, forming only about one-half of one per cent, of malig- 
nant growths.^ 

Macroscopically, the tumors are interesting as showing 
a great variation in the amount of pigment. The primary 
tumor and its metastases may be coal black; the tumor 
may be mottled brown and white, or it may contain only 
a few dark areas. The metastases from a black tumor may 
be perfectly white; or metastases from a light tumor may 
be intensely pigmented. The nature of the pigment is not 
fully understood.2 It does not contain iron, and varies a 
good deal in the intensity of color, being either black, or 
brown, or even yellowish.^ The granules may be either 
large or small. They are frequently phagocyted by neigh- 
boring cells of the connective-tissue group, which then 
carry the pigment about the body, and as the cells con- 
taining it die, the pigment goes into solution and appears 
in the blood and urine, giving the latter fluid a brownish 
or blackish color. 

Microscopically, the early melanomata resemble very 
closely the tissue from which they have been derived ; that 
is, they are formed of small masses of oval or spherical 
cells, with large vesicular nuclei, sometimes double. These 
cells may or may not be separated from each other by con- 
nective tissue, and about and among them lie scattered pig- 
mented connective-tissue cells, the so-called chromato- 
phores. The amount of pigment varies ; it is often so great 
as to obscure the cell nucleus. The tumors arising in the 
skin often resemble the carcinomata in morphology.* The 

^Lanwers: Miinch. med. Wchnschr., 1911, Ixviii, 215. 

2Hada: Virchows Arch, f, path. Anat., 1914, ccxv, ZIQ. 

3See, for chemical studies, W^ells: Chemical Pathology, 3d ed., Phila- 
delphia, 1918, and von Fiirth: Probleme der physiologischen und pa- 
thologischen Chemie, Leipzig, 1912. 

^Broders and MacCarty: Surg., Gynec, and Obst., 1916, xxiii, 1; 
Gilchrist: Jour. Cutan. Dis., 1899, xvii, 117; Johnston: ibid, 1905, xxiii, 
1. For a summary of the discussion as to the origin of the cells of the 
melanomata, see Dalla Favera: Zieglers Beitr., 1903, xliii, 43. 

127 



large spherical cells lie in nests in close juxtaposition to 
each other with no intervening connective tissue, so that 
they often seem molded by pressure into hexagonal forms 
with rounded angles. On the other hand, the tumors of 
the choroid, iris, and ciliary body, and the primary mela- 
nomata of nerve trunks are distinctly sarcomatous in their 
structure, the cells lying in and closely related to the con- 
nective tissue. In the epithelial type, pigment is often seen 
in the epithelial cells, even in those undergoing mitosis, and 
is seems probable that this pigment is related to the pig- 
ment normally present in the basal layer of the skin 
epithelium. Usually, however, chromatophores are also 
present, and Ribbert's view is that these cells are the 
specific element of the tumor, which should therefore be 
called a chromatophoroma, and that the epithelium is en- 
tirely subsidiary, even if present. Nevertheless, an instance 
is recorded in which the epithelial type of tumor showed 
distinct keratinization.^ In the sarcomatous type, the 
spindle cells of the sarcoma carry more or less pigment. 
Some areas may be entirely free, but in others heavily pig- 
mented cells are present. Free pigment occurs also in 
both types, lying in the connective tissue stroma of the 
tumor. Clinically, the melanomata form rounded, lobulated, 
black or brown or irregularly colored masses, which project 
from the surface and often ulcerate as the growth extends. 
The surface epidermis may remain while the tumor be- 
neath it softens so that the patient may state that the 
tumor began in a "blood blister." The consistency of the 
tumor varies a good deal, both in the primary growth and 
the metastatic nodules. Many of the tumors are quite firm 
and but little material can be scraped from the surface. 
Others are softer, and some almost diffluent, so that a 
brownish paste can be scraped from the surface. 

^Beckey: Frankfurt. Ztschr. f. Path., 1915, xvii, 365. 

128 



The diagnosis can be made in many instances merely 
by inspection, any rapidly growing black tumor may safely 
assumed to be a melanoma, though a black necrotic crust 
is sometimes seen over granulomata, and this may mislead 
an inexpert observer. Occasionally, where the nodules are 
not much pigmented, careful microscopical examination 
will reveal the typical structures which are characteristic 
of mole tumors. The malignancy or benignancy of irritated 
moles may not, however, be easy to determine. Abundant 
mitoses and deep invasion of the corium point strongly 
toward a dangerous lesion. Small seed-like metastases 
near the primary growth are absolute evidence. 

Occasionally the presence of blood pigment in a sar- 
coma or in a granuloma may lead to the suspicion that the 
tumor is of melanotic origin; but, as a rule, this pigment 
which is derived from the blood gives an iron reaction 
when treated with dilute hydrochloric acid and potassium 
ferrocyanide, while melanin does not react to this test. In 
tissues fixed with formaldehyde, fine blackish granules 
occasionally appear, and may lead to some confusion; but 
as they are soluble in dilute alcoholic alkalies, and are also 
frequently found in the lumen of the vessels in the serum 
coagulated by the fixative, differentiation should not be 
difficult. 

TUMORS OF ENDOTHELIUM 

ENDOTHELIOMA 

The endotheliomata are tumors derived from endo- 
thelium as the specific element of their structure. In the 
past a large number of growths were classified under this 
heading; but with more careful study of the histological 
derivation of tumor cells, the group has grown smaller and 

129 



smaller until now only a very few tumors are recognized 
as properly belonging to it.^ Those who have studied the 
subject have found it more and more difficult to prove 
definitely that the tumor was derived from endothelium, 
for the mere continuity of the tumor cells with the lymph- 
vessel endothelium at the periphery of the growth is no 
proof of the identity of the tumor cell and the endothelial 
cells. Borst and others, for example, have shown that 
tumor cells may line such channels and grow under or over 
the endothelial cells. Recent embryological studies of the 
derivation of the cells lining the pleural, pericardial and 
peritoneal cavities have led to the conclusion that these cells 
are epithelial or mesothelial in origin, and not endothelium '^ 
and, hence, the tumors derived from these cells must be 
regarded as carcinomata, and not as endotheliomata. So, 
too, the large group of the complex tumors appearing in the 
salivary glands have of late years been excluded from the 
endotheliomata and shown to be composed of modified 
epithelium with a complex mesoblastic stroma. 

Of the tumors generally acknowledged to be derived 
from endothelium, those of the blood-vessels are perhaps 
the most satisfactory representatives. These neoplasms, 
however, are very rare. Two tumors composed chiefly of 
blood-channels lined with endothelium have been de- 
scribed f and a metastasizing tumor of the penis which was 
composed of blood-channels lined with endothelial cells also 
has been reported.* Another tumor in the liver, composed 

^For an interesting discussion of a mixed tumor of the lachrymal 
gland, which reveals many of the difficulties of the older morphologists, 
see Koester: Cancroid mit hyaliner Degeneration (Cylindroma Billroth's) 
Virchows Arch., 1867, xl, 468. See, also, Volkmann: Deutsch. Ztschr. f. 
Chir., 1895, xli, 1. 

^Minot: Science, 1901, xiii, 481; Miller and Wynne: Jour. Path, and 
Bacteriol., 1908, xii, 267; Monckeberg: Zieglers Beitr., 1903, xxxiv, 489; 
Benda: Deutsch. med. Wchnschr., 1897, xxiii, 324. 

sBorrmann: Lubarsch-Ostertag, Ergebn. d. allg. Path,, 1900-01, vii, 
888; Virchows Arch., 1898, cli, Suppl., 151; 1899, civil, 297. 

^Colmers: Zeiglers Beitr., 1903, xxxiv, 295. 

130 



of dilated capillaries with thickening of the endothelium 
which often formed small nodules has been put into this 
class.^ 

A benign growth of the inner surface of the pulmonary- 
vein which also may be included here, has been described.^ 
Other examples of intravascular tumors are a few which 
have been reported as growing in the hemorrhoidal veins; 
but great caution should be exerted in accepting these with- 
out further proof. The thrombi which regularly occur in 
these vessels are very frequently completely surrounded 
and infiltrated with endothelium and may give rise to a 
tumor-like mass without being anything more than a rather 
advanced state of reparative overgrowth. Certain of the 
very vascular bone tumors have been considered as endo- 
thelioma ; these form soft, richly vascular pulsating masses, 
which grow slowly and may ultimately absorb the bone and 
cause spontaneous fracture. At the present time most of 
these tumors are classed with the angiosarcomata. Some 
are unquestionably hypernephromata metastasizing from a 
small primary tumor which has given no clinical signs and 
has thus passed unrecognized.^ Others may more properly 
belong in the class of angiomata.* 

A certain number of large-cell tumors arising appar- 
ently in the lymph-node have been considered as endothelial 
in origin, but many of these growths unquestionably are 
atypical Hodgkin's disease,^ and others are secondary car- 
cinomata. 

Psammomata — It is generally acknowledged that the 
cells lining the spaces of the dura, pia, and arachnoid, or 

^Fischer: Frankfurt. Ztschr. f. Path., 1913, xii, 399. 

^Sailer: Contributions from the William Pepper Laboratory of Clini- 
cal Medicine, University of Penn., 1900, (Abstr. in Centralbl. f. allff. 
Path., 1901, xii, 263); Unruh: Deutsch. med. Wchnschr., 1896, xxii, 746. 

^Marckwald: Virchows Arch., 1895, cxli, 12:8. 

*Narath: Langenbeck, Arch. f. klin. Chir., 1895, 1, 794. 

f^Ewing: Jour. Med. Research, 1913, N. S. xxiii, 1. 

131 



forming small accumulations in these membranes, are of 
endothelial nature, and at present there is no widespread 
objection to the designation as endotheliomata of tumors 
of this origin. The psammomata are among the most fre- 
quent brain tumors. They are usually attached to the dura 
either by a pedicle or by a broad base, but sometimes are 
wholly free from this membrane. They form flat, oval or 
spherical growths of a greyish red color, with a well marked 
capsule in which lie many vessels of considerable size. The 
tumor, despite its bulk, does not, as a rule, tend to erode 
the bone, and therefore presses into the brain substance; 
but as it does not infiltrate and is slow growing, no clinical 
symptoms are noted unless it reaches a large size. Small 
tumors are most often found accidentally post mortem. 
They are usually single, but may be multiple, grow very 
slowly, and do not metastasize. Similar tumors are found 
on the dural sheath of the optic nerve, in the pia, in the 
pineal gland, and in the choroid plexus; while some of a 
different type appear in the peritoneal cavity and ovary 
(psammocarcinoma) . 

Microscopically, these tumors consist of a loose tissue, 
often fairly vascular, in which lie irregular masses of flat- 
tened spindle-shaped or polyhedral cells. These cells tend 
to form whorls which may contain a small blood-vessel at 
the center. Ultimately, such masses of cells undergo de- 
generation with the deposition of calcified material in the 
necrosed area. The lime is deposited in lamellae and the 
globules so formed usually have a darker staining cortical 
portion with a clear central part. Mallory believes that 
elastic or hyaline collagen fibers are the site of the calcium 
deposits. Calcification occurs, also, in the interstitial con- 
nective tissue, which is especially liable to hyaline degener- 
ation. 

The diagnosis of these dural tumors is quite easy, even 
in the gross, for if the psammoma bodies are well developed 

132 



the tumors, when incised, have a gritty feel, which is char- 
acteristic. Microscopically, even if no calcification has 
taken place, the morphology is absolutely different from 
that of any other tumor, though, as has been said, similar 
growths have been seen in the ovary and in the peritoneal 
cavity. An inflammatory process resembling a psammoma 
is very rarely seen in chronic inflammation of the omentum, 
in which psammoma bodies form in the lymphatics, the 
so-called peritonitis arenosa. 

TUMORS DERIVED FROM NERVE STRUCTURES 

GLIOMA 

The gliomata are tumors composed chiefly of the sup- 
porting substance of the central nervous system or neuro- 
glia. Tumors of this type can occur only in the brain, the 
spinal column, and the roots of the cranial nerves, or in 
sites, such as the root of the nose, where gliar tissue has 
been left during embryonic development.^ Gliomatous 
tumors are found, also, in the eye coming from the retinal 
interstitial tissue. The cells in all these tumors, however, 
are not of the same type, a smaller or larger portion often 
resembling the ependymal epithelium. Such tumors are 
more accurately designated neuroepitheliomata or spongio- 
blastomata. Inasmuch, however, as the true glia is de- 
rived from cells of this type, both forms of tumor may be 
considered together. 

The gliomata of the brain are diffuse masses of new 
formed tissue which can often scarcely be distinguished 
from the brain substance itself. If the blood supply is rich 
they have a greyish red color which distinguishes them 

^Schmidt, M. B.: Virchows Arch. f. path. Anat., 1900, clxii, 340; Clark: 
Am. Jour. Med. Sc. 1905, cxxix, 769 

133 



from the gray of the brain substance. Usually, however, 
secondary changes with necrosis, edema, and hemorrhage 
occur in the central portions of the growth, so that the 
approximate boundaries of the tumor can be made out. 
As a rule, the tumors are softer than the brain substance; 
occasionally, however, they are quite hard. When necrotic, 
the tissue assumes a yellowish cloudy appearance due to 
the absorption of blood pigment from the extravasation 
which takes place in the necrosed areas. In a later stage 
of this process, a tumor may be found with a central cyst 
caused by a breaking down of the central portion, only the 
periphery showing well preserved cells. Occasionally, in- 
stead of occupying the brain substance, the tumor may 
project into the ventricles and may even be pedunculated. 

A second type is occasionally seen in which the tumor 
is merely a circumscribed hardening, thickening, and par- 
tial obliteration of a few convolutions with the underlying 
white substance. In this case it is difficult to speak of a 
tumor, the condition seems to be rather a diffuse glio- 
matous transformation of the brain substance. 

The gliomata of the spinal cord form circumscribed 
nodules or long spindle-shaped tumors surrounding the cen- 
tral canal. They are usually surrounded by a white sub- 
stance. The central canal may be dilated, and the interior 
of the cyst may become softened, and the condition be mis- 
taken for syringomyelia. The gliomata of the retina spread 
into the vitreous as nodular growths. Rarely they pene- 
trate the sclera and appear in the external surface of the 
eye. On gross section they are grayish and have a soft 
consistency. 

The gliomata may be regarded as to a certain extent 
malignant, though, except in rare instances, they do not 
form metastases at a distance.^ Local recurrences, how- 

*Jacob: Jour. Med. Research, 1916, N. S., xxix, 95 (glioma of cere- 
beUum with, metastases). 

134 



ever, are frequent. In general the growth of the tumor 
is slow, and in the brain the symptoms are often those of 
apoplexy. Gliomata of the eye occasionally form metastatic 
nodules in the cranial cavity, and invasion of the lymph- 
nodes of the neck has been frequently noted. 

The microscopical structure of the gliomata is in many 
cases characteristic.^ The cells of the tumor are composed 
of the spider cells (astrocytes) with large oval nuclei and 
very small bodies, the latter sending out into the tissues a 
variable number of projections which form a dense mesh- 
work about the cells. In many tumors, however, the glia 
cells do not assume in all cases their characteristic type, 
but may form large irregular cells with large nuclei, 
resembling to a certain extent ganglion cells. Two or three 
nuclei may be present in the same cell. Occasionally the 
spindle-cell type predominates and the fibrils are then 
parallel to each other, lying in one direction, a picture which 
suggests a spindle-cell sarcoma, especially if the fibrillar 
structure is not well developed. The peripheral growth into 
the surrounding tissues is slow, corresponding to the slow 
development in the size of the tumor, and the boundaries 
can be determined only by the greater richness of the 
tumor tissue as compared to the surrounding brain tissue. 
The cells of the brain are destroyed by the gradual growth 
of the cells of the tumor and are occasionally found in the 
periphery of the same as irregularly contoured cells, the 
nuclei of which stain but faintly. The nerve fibers, like- 
wise, are gradually destroyed. When the tumor involves the 
pia, the cells penetrate the lymphatics and closely surround 
the smaller vessels. Occasionally the epithelial type of the 
tumor becomes predominant, and alveoli lined with epithe- 
lium of the same type as that of the central canal of the 

*See, for histological details, Stroebe: Zieglers Beitr., 1895, xviii, 405. 

135 



cord and the cavities of the brain may be found inter- 
mingled with typical glia cells.^ Tumors of this type, 
spongioblastomata, seem especially abundant in the cere- 
bellum. The microscopical structure of the gliomata of the 
spinal cord is the same as that of the gliomata occurring in 
the brain. 

Gliomata described as occurring in the adrenal are 
probably neuroblastomata.^ 

Gliomata of the eye^ show a somewhat different struc- 
ture from those of the brain and cord. They are composed 
chiefly of cells with large oval nuclei possessing but little 
cell body, and often show no development of the fibrils 
characteristic of the gliomata in other places. They very 
frequently undergo necrosis, only the cells of those portions 
of the growth which are close to the blood-vessels being 
preserved. The protoplasm is often very soft and without 
sharp outlines, and the tumor resembles a sarcoma much 
more than a glioma of the central nervous system. The 
rosette-like structures composed of cylindrical cells ar- 
ranged in a radial manner about a small lumen occur in 
about half the cases. In the recurrences the cells are still 
less characteristic and resemble most closely large lympho- 
cytes. 

The retina may be pushed forward or involved in the 
tumor. It is probable that all of these tumors arise on the 
basis of a congenital defect. Many if not all of them appear 
in early life (80 per cent, during the first three years) ; 
some have been found at the time of birth ; and in the case 
of gliomata of the eye about one-fourth of the cases have 
been bilateral. It has also been noted that the tumors may 

iRibbert: Virchows Arch. f. path, Anat., 1918, ccxxv, 195. 

2Schilder: Frankfurt. Ztschr. f. Path., 1909, iii, 317; Wiesel: Vir- 
chows Arch. f. path. Anat., 1905, clxxx, 553; Wri&ht: Jour. Exper. Med., 
1910, xii, 556. 

'Wintersteiner: Das Neuroepithelioma retinae, Vienna, 1897 (mono- 
graphic study of 467 cases). 

136 



be found in several children of a family, or in those whose 
parents have had retinal gliomata. This is one of the best 
examples of the inheritance of embryonic defects leading 
to tumor production.^ 

The clinical course of all the gliomata is progressive 
and they ultimately lead to the death of the host, even if 
the tumors do not metastasize. 

In addition to the gliomata, which arise from the 
specific supporting tissue of the brain, spindle-cell sarcoma 
may originate from the connective tissue which follows the 
vessels in from the surface. This is, however, an infre- 
quent occurrence. 

TUMORS OF NERVE CELLS AND THEIR 
ANTECEDENTS 

The tumors which are derived from the embryonal 
antecedents of the nerve cells or from the fully developed 
elements form an interesting group whose exact classifica- 
tion is still somewhat in doubt, partly because of lack of 
sufficient histological means of differentiation, and partly 
since, owing to the great rarity of the tumors, but little 
material has been available for study of the morphological, 
biological, or other characters of these neoplasms. 

The histological derivation of the tumors is as follows i^ 
The neural ectoderm gives rise to the spongioblasts which 
form glia, to the neuroblasts which form the ganglion cells 
of the brain and cord, and to the neurocytes of the sympa- 
thetic system. The last are equivalent to the sympatho- 
gonia, which by further development give rise to the 
sympathoblasts or ganglion cells of the sympathetic 

^Griffith: Brit. Med. Jour., 1917, i, 850; Hansell: Am. Jour. Dis. Child., 
1915, ix, 485. 

2Landau: Frankfurt. Ztschr. f. Path., 1912, xi, 26; Wahl: Jour. Med. 
Research, 1914, N. S., xxv, 205. 

137 



nervous system, and to the phaochromoblasts or chromaffin 
cells which form a portion of the structures of the endo- 
crine organs which are intimately connected with the sym- 
pathetic. Theoretically, tumors may arise from any one of 
these groups of cells. 

Neurocytoma 

Only one tumor thought to be derived from neurocytes 
(a neurocytoma) has been described.^ It was situated in 
the Gasserian ganglion and consisted of masses of entirely 
uncharacteristic round or oval cells. There were no fibrils 
present, the growth thus resembling the neurocytes of the 
embryonal nervous system. 

Neuroblastoma 

The sympathogonion stage in the development of the 
nervous system is represented in the tumor group by the 
neuroblastoma (neuroepithelioma of some authors) .^ 
Tumors of this type theoretically may involve any part of 
the nervous system, though they usually occur in the 
adrenal region, in connection with the sympathetic system. 
They are highly malignant growths which not infre- 
quently metastasize into the liver, bones, and lymph-nodes. 
Usually they occur in infants, and the less the differentia- 
tion of the histological elements the greater the degree of 
malignancy.^ 

iMarchand: Festschrift fur Rindfleisch, 1907. 

^Lehman, E. P.: Jour, Med. Research, 1917, N. S., xxxi, 309 (bibl.). 
Lambert, R. A.: Proc. New York Path. Soc, 1917, xvii, 96 (bibl.). For 
an earlier review of the literature, see Wright, J. H. ; Jour. Exper. 
Med., 1910, xii, 556 (Wright uses neurocytoma and neuroblastoma as 
synonymous). See, also, Symmers: Jour. Am. Med. Assn., 1913, Ix, 337. 

sHerxheimer: Zieglers Beitr., 1914, Ivii, 112 (bibl.); Freifeld: ibid., 
1915, Ix. 347 (bibl.). 

138 



In the gross, the tumors may be very large and may 
occupy a considerable portion of the abdomen of the in- 
fant. The surface is usually smooth, from the pushing for- 
ward of the peritoneum, behind which the tumors lie. On 
section they show a great variety of structures, in some 
places being formed of soft, gelatinous connective tissue, 
in others being somewhat firmer. In color, they are usually 
dark reddish, or irregularly mottled. 

Microscopically, these tumors are made up of varying 
areas; some of these contain small cells with deeply stain- 
ing nuclei which tend to arrange themselves in little globu- 
lar masses, the centers containing a feltwork of fine fibrils. 
Scattered throughout the mass there are apt to be, also, 
fibrils of different types. In some instances, in addition, 
there are areas of well formed ganglion cells showing fibrils 
and multiple nuclei, embryonic connective tissue, fat, and 
mucous tissue. Hemorrhagic and necrotic portions are not 
infrequent. 

The diagnosis is impossible except with the micro- 
scope. The characteristic rosettes already described and the 
demonstration of ganglion cells give a clue to the condi- 
tion. If neither of these structures is present, it is difficult 
not to place the tumor in the class of small-cell sarcomata, 
to which undoubtedly many of them have heretofore been 
assigned. These tumors should be carefully distinguished 
from the congenital mixed tumors of the kidney which 
contain muscle fibers, remnants of developing kidney struc- 
ture, sarcomatous fractions, fat, and embryonic connective 
tissue. 

Sympathoblastoma 

Only one tumor of the sympathoblastoma group has 
been discovered. This was found in the cervical sympa- 
thetic of a child, and was made up of cells somewhat larger 

139 



than the embryonic sympathogonia. Between the cells lay 
a fine fibrillar substance which was regarded as composed 
of neurofibrils. Another small tumor nearby contained 
ganglion cells and nerve fibers ; hence, it must be considered 
as a ganglioneuroma.^ 

Ganglioneuroma 

The next phase in the development of the nervous 
system consists in the formation of ganglion cells. New 
growths are, however, rarely composed solely of these ele- 
ments, but are apt to contain cells representing some or all 
phases of the development of the neurocyte.^ They occur 
not only in children, but in adults, but are rather rare after 
the age of forty. They are, as a rule, fairly benign, though 
if they contain immature elements, they may be quite 
malignant. The younger the patient bearing the tumor the 
more malignant the growth is apt to prove. The tumors 
may arise anywhere in the nervous system, though most 
of them involve the sympathetic, and especially the ab- 
dominal portion. In addition, they have been found involv- 
ing the peripheral nerves, in the adrenal, the cerebral 
nerves, the brain, and the cerebral ganglia, and also in the 
medulla.^ In all, some fifty cases have been recorded. The 
tumors are usually encapsulated, soft, and on cut section of 
a dark reddish color. 

Microscopically, they contain ganglion cells, as a rule 
fairly well developed, lying in a tissue composed of nerve 

iMartius: Frankfurt. Ztschr. f. Path., 1913, xii, 442. 

2Wahl: Jour. Med. Research, 1914, N. S., xxv, 205; Landau: Frank- 
furt. Ztschr. f. Path., 1912, xi, 26; Peters: ibid., 1913, xiii, 114; Freund: 
ibid., 1913, xiii, 266; Robertson: Virchows Arch. f. path. Anat., 1915, 
ccxx, 147; Falk: Zieglers Beitr., 1907, xl, 601. 

3Dunn: Jour. Path, and Bacteriol., 1914-15, xix, 456 (bibl.). 

140 



fibrils, usually non-medullated. In addition, small cells re- 
sembling lymphocytes and larger elements with vesicular 
nuclei corresponding to sympathogonia and to sympatho- 
blasts are also present in the tumor. Glia, also, is not in- 
frequent. Metastases have occurred in the liver and the 
neighboring lymph-nodes. The tumors are derived from 
embryonal displacements of nerve tissue, as is shown by 
their occasional multiplicity and by their relation to other 
lesions of the nervous system. 

Paraganglioma (Phaochromoblastoma or Chromaffin 
Tumors) 

The rare neoplasms of this group are composed of 
chromaffin cells. They occur chiefly in the medulla of the 
adrenal and in the carotid gland. The chromaffin tumors of 
the adrenal are very rare, only some twelve cases having 
been described. They are small and are usually discovered 
accidentally at autopsy. Like the tumors just described, 
the adrenal paragangliomata contain cells in various stages 
of differentiation. The predominating elements are large 
cells resembling epithelium, in which with suitable stains 
and reagents adrenalin and glycogen can often be demon- 
strated. They assume after proper fixation with chrome 
salts the brown stain which is characteristic of the chro- 
maffin substance, though not infrequently this reaction is 
faint or missing.^ These tumors are not infrequently asso- 
ciated with neurofibromatosis, and, therefore, may be 
viewed as one manifestation of a disturbance of the entire 
nervous system. 

iWahl: Jour. Med. Research, 1914, N. S., xxv, 205; Harbitz: Arch. 
Int. Med., 1915, xvi, 312. 

141 



Paragangliomata of the Carotid Gland^ 

The tumors form small, rounded, lobulated, encapsu- 
lated masses at the bifurcation of the carotid artery which 
is often surrounded and compressed by the growth. They 
are quite vascular and soft, and on section reddish or 
brownish, or when fixed in chrome salts show the brown 
color of the chromaffin substance. The growth is slow. 
In general, the tumors are slow growing and benign, though 
several recurrences have been noted following operation, 
and the cervical lymph-nodes have been found involved.- 

The structure resembles that of the carotid gland and 
consists of alveoli bounded by connective tissue with abun- 
dant capillaries and containing cuboidal, round, or oval cells 
with a fairly abundant cytoplasm. These cells, when prop- 
erly preserved, show chromaffin substance in the cytoplasm. 
Giant cells and syncytial buds or masses have occasionally 
been described. Traces of non-medullated nerve fibers, and, 
in one instance, ganglion cells have been found in the 
tumor. 

Neuroma 

The term neuroma should properly be restricted to 
tumors formed of nerve tissue, though in the past it has 
been used rather loosely to describe many of the fibromata 
of the nerve trunks and the so-called amputation neuro- 
mata, which are merely tangled masses of nerve fibers 
found in the stump of amputated nerves and are the 
result of regenerative processes, not true tumors. The 

iPaltauf: Zieglers Beitr., 1892, xi, 260; Monckeberg: ibid., 1905, 
xxxviii, 1; Keene and Funke: Jour, Am. Med. Assn., 1906, xlvii, 469; 
Callison and Mackenty: Ann. Surg-., 1913, Iviii, 740; Balfour and Wild- 
ner: Surg-., Gynec, and Obst., 1914, xviii, 203; Gronemann: Virchows 
Arch. f. path. Anat., 1914, ccxviii, 163 (bibl.). 

^Kauffmann and Ruppanner: Deutsch. Ztschr. f. Chir., 1905, Ixxx, 259 
(bibl.) 

142 



ganglioneuroma has already been described. The fibrillar 
neuroma is an exceedingly rare tumor, consisting of intri- 
cately intertwined medullated or non-medullated nerve 
fibers.^ In the nerve fibers lie long oval nuclei, and between 
them is a small amount of connective tissue. The neoplasms 
occur as small nodules chiefly in the skin. Unless nerve 
fibers can be identified by specific stains the tumor must be 
regarded as false neuroma or neurofibroma. 

TUMORS OF EPITHELIUM AND CONNECTIVE TISSUE 

PAPILLOMA 

A papilloma is a fibro-epithelial tumor of the skin or 
mucous membrane, of a flat or elevated shape, in which the 
epithelium forms a considerable portion of the growth and 
shows no tendency to invade the deeper connective tissue. 
The dermal papillomata must be distinguished from the 
papillary fibromata of the skin and from the polypoid or 
papillomatous tumors which spring from the mucous mem- 
branes of the nose, uterus, bladder, and gastrointestinal 
tract. They can be differentiated from the fibromata by 
the fact that in the latter the epidermis covering the growth 
is not an integral portion of it, but merely skin overlying 
a tumor of connective tissue ; while in the true papillomata 
the epithelium is an integral part of the tumor and is in 
close contact with the more or less hypertrophied connec- 
tive tissue. The polypi of the nose are, in many instances, 
myxofibromata with a thin covering of epithelium, and pos- 
sibly a few mucous glands, while the polypoid growths from 
the endometrium and the gastrointestinal tract are largely 
composed of hyperplastic glandular tissue and are less char- 
acteristically fibro-epithelial. 

^Bruce and Dawson: Rev. Neurol, and Psychiat., 1913, xi, 117; 
Knauss: Virchows Arch. f. path. Anat., 1898, cliii, 29. 

143 



Papillomata may occur in any portion of the body cov- 
ered by flat epithelium, and also on the mucous membrane 
of the mouth, tongue, pharynx, larynx, vagina, pelvis 
of kidney, ureter or bladder. The sites of special fre- 
quency of the most common dermal variety, the wart, are 
the face, hands, and genital regions; while the most fre- 
quent sites of the internal type are the bladder, the intes- 
tine, and the surface of the ovary. The true papillomata, 
both of the skin and in the bladder, may be congenital and 
multiple. The ordinary wart is thought by some dermatolo- 
gists to be of infectious origin. 

A special type of papilloma is that due to irritation 
by inflammatory exudates of the skin about the genital 
regions, the so-called condyloma. 

The papillomata may be minute, almost microscopic, 
or they may be of very considerable size. The writer has 
seen on the glans penis a globular tumor of this variety, 
some 10 cm. in diameter. The surface may be very irre- 
gular, rounded, or pointed, and divided by fissures into a 
cauliflower-like excrescence. The peduncle may be long or 
very short and broad. Condylomata are pointed or even 
divided into tufts. Infection is common, with the forma- 
tion of a serous or purulent exudate or a dry necrotic crust. 
If the surface epithelium is not removed by washing or 
mechanical friction it may become much thickened and form 
a cutaneous horn, occasionally several centimeters in length. 

In the bladder and rectum the papillomata form polyps, 
that is, the pedicle is apt to be long so that the tumor is 
freer than the sessile verruca. The surface is irregular 
and reddish, and the tumors occurring in the bladder are 
often covered with a sloughy coat which may contain de- 
posits of insoluble phosphates. The interstitial form may 
necrose from torsion of the pedicle. The ovarian papillo- 
mata are usually considered as a part of an adenomatous 

144 



or carcinomatous growth of that organ, being merely papil- 
lary in form when growing freely from the surface. 

Under the microscope, the dermal papillomata show a 
layer of cornified epithelium, often thrown into very irre- 
gular folds and projecting into the connective tissue, but 
no individual cells penetrating deeper, with a firm base- 
ment membrane separating the two types of tissue. The 
lower layers of epithehum may be pigmented; the upper 
layers may show a more or less extensive cornification. 
The connective tissue is generally dense and contains but 
few blood-vessels. 

Clinically, the dermal papillomata, with rare excep- 
tions, are quite benign; those from the bladder, intestine, 
and ovary may be either benign or malignant ; the differen- 
tiation can be made only by careful microscopic study, and 
sometimes even this fails.^ Laryngeal and lingual papillo- 
mata are always to be regarded with suspicion. 

Usually there is no difficulty in diagnosing the ordinary 
type of papilloma, but when the growth has been inflamed 
by irritation and the subepithelial connective tissue has 
become softened, edematous, and infiltrated with cells, there 
may be a loosening of some of the epidermal elements, and 
the growth may suggest an epithelioma. An abundance of 
mitoses in the epithelium may be found in inflamed warts. 
The differential diagnosis is especially difficult in cases of 
papillomata of the glans penis, where it is sometimes impos- 
sible to determine whether the tumor is malignant or not. 
Apparently these growths begin as benign tumors, but 
chronic inflammation sets up epithelial proliferation which 
may finally result in an alteration in the type of growth 
which then penetrates the corium more deeply. Usually, 
however, it is possible to make a correct diagnosis from the 

^Buerger: Surg-., Gynec, and Obst., 1915, xxi, 179; Syring: Beitr. z. 
klin. Chir., 1911, Ixxiii, 66; Vers6: Arb. a. d. path. Inst, zu Leipzig, 
1908, i. No. 5. 

145 



absence of mitotic figures in the papilloma and from the 
lack of generalized invasion of the deeper tissues. The 
lingual papillomata, also, offer diagnostic difficulties, as a 
considerable proportion of the carcinomata have a papillary 
stage preceding ulceration and deep invasion of the muscle. 
The careful study of sections from the base of the tumor 
is often necessary. Considerable difficulty may be met 
with, also, in tumors from the mucous membrane of the 
bladder. From his own experience, the writer is inclined 
to call almost all tumors of the bladder malignant unless 
there is definite evidence to the contrary. The papillary 
carcinomata have much the same structure as the papillo- 
mata and it is often impossible, owing to the operative dif- 
ficulties in removal of the pedicle of the tumor, to find suit- 
able portions of the connective tissue substratum to deter- 
mine whether invasion by epithelial cells has taken place. 
Too often merely a fragment is pulled off the top of such 
a tumor, and the pathologist is requested to decide as to its 
nature. 

Points of importance in diagnosis are: (1) type of cell, 
which in the papillomata is small and cylindrical with a 
nucleus fairly poor in chromatin, while in the carcinomata 
it is large, vesicular, and rich in chromatin, and often shows 
mitoses; (2) type of basement membrane, which in the 
papillomata is well marked, in distinction to the irregular 
line or diffuse invasion in the carcinoma. Occasionally a 
positive diagnosis is impossible and reliance, must be placed 
more on the clinical appearances of the growths, those with 
broad short pedicles being more apt to be malignant than 
the long necked, thin variety. About half of the intestinal 
polypi ultimately become malignant; while the ovarian 
tumors invade the peritoneum in a majority of instances. 

146 



Naevus or Mole 

The exact classification of these congenital defects is 
not yet settled, because the nature of the characteristic 
cells which form the chief portion of the mass is still un- 
determined, although many pathologists are at present in- 
clined to assume that they are epithelial in origin. There- 
fore, they may be described in connection with the fibro- 
epithelial tumors of the skin or with the tumors from mela- 
notic tissues. Nsevi are of two types, either pigmented or 
non-pigmented, the former being much the more common.^ 
They occur everywhere on the body, and hardly any indi- 
vidual is exempt from one or two. The most frequent site 
is the skin of the face and neck, but other portions of the 
integument are often affected. They may be small, measur- 
ing only a few millim.eters in diameter, or may cover large 
portions of the body.^ Some of them are perfectly smooth, 
slightly elevated tumors; others are pedunculated and 
rough; some are covered with hair and are deeply pig- 
mented. Occasionally nsevi are extremely rich in blood-ves- 
sels, so as to make a combination of angioma and nsevus- 
cell tumor ; or they may contain much fat (nsevus lipomato- 
des). The skin overlying the tumor is usually irregular in 
thickness, as a rule, thinner than normal, and may send 
down papillary processes between the areas of naevus cells. 
The pigment melanin is often contained in the nsevus cells, 
even when they retain their spherical or oval form, but is 
also seen in a branching, flattened cell known as a chromato- 
phore, which is considered by Ribbert to be of connective- 
tissue origin.^ Nsevi consisting almost entirely of chromato- 

^See, for classification and morphology, Moller: Arch, f. Derm. u. 
Syph., 1902, Ixii, 55 and 371; Riecke: ibid., 1903, Ixv, 65. 

2Fox, H.: Jour. Am. Med. Assn., 1912, Iviii, 1190. 

^For details concerning- the origin of the naevus cells, see Dalla 
Favera: Zieglers Beitr., 1908, xlii, 43. 

147 



phores have been described in a few instances.^ The vast 
majority of naevi are very unimportant skin blemishes, and 
remain quiescent throughout life ; but occasionally, owing to 
some unknown cause, possibly chronic irritation, a melano- 
epithelioma or melanosarcoma develops in a nsevus with 
serious results. ^ Such tumors show a characteristic mor- 
phology and, even if not pigmented, can be recognized in 
most instances as a mole derivative.^ 



ODONTOMA 



An odontoma is a tumor arising in the jaws from rem- 
nants of the structures which form the teeth. These com- 
prise an epithelial cap covering a connective tissue papilla, 
the former furnishing the enamel organ, the latter the 
dentine or pulp. Hence several forms of solid or cystic 
tumors may be expected to occur in this region. One is 
the epithelial odontoma or adamantinoma arising from the 
adamantine organ, another is the fibrous or cemental odon- 
toma, w^hich is derived from the mesoblastic structures; 
while the third form includes cystic growths of various 
types. A complete and satisfactory classification of the 
three groups has not yet been worked out. 

Adamantinomata are tumors which arise from rem- 
nants of the enamel organ left during the formation of the 
teeth; though in a few instances the neoplasm has been 
thought to be derived from the alveolar epithelium.^ They 
occur in young adults, as a rule, and most frequently in the 
region of the molar teeth of the lower jaw. The tumors 

iTieche: Vircho-ws Arch. f. path. Anat., 1906, clsxxvi, 212, 

^Green: Virchows Arch. f. path. Anat., 1893, cxxxiv, 331; Waelsch: 
Arch. f. Derm. u. Syph., 1899, xlix, 2-i9. 

^For further details see the section on tumors of the melanotic 
tissues. 

^Krompecher: Zieglers Beitr., 1918, Ixiv, 165. 



148 



usually are slow-growing, may reach a very great size, and 
are intimately connected with the bone of the jaw. The 
growth may be cystic, partially solid and partially cystic, 
or all solid. The portion of the bone in which the tumor 
is situated is usually rarefied and often forms merely a 
thin layer over the tumor. The cut section of the growth is 
whitish and granular, and a granular material can be 
scraped from it with a knife. 

Microscopically, the tumor assumes two forms: one, a 
cystic type with the alveoli occasionally lined with high 
cylindrical cells; the other, a solid or medullary form in 
which the alveoli are filled with peculiar stellate cells char- 
acteristic of the enamel organ. The external layer of cells 
may be more or less flat and lose the stellate form. Pearl- 
like bodies are rarely seen. As a rule, the tumors of this 
type are benign and do not recur after excision, but occa- 
sionally recurrences are noted and in some instances have 
been followed by metastases in the bones of the skull at a 
considerable distance from the original site.^ An exception 
to the rule that all adamantinomata are found in the jaws 
has been reported, a tumor of this morphology having been 
found in the tibia.^ This curious instance of heterotopia 
was explained by the assumption that there was a con- 
genital malformation by which enamel tissue was produced 
in the tibia. 

The connective-tissue odontomata are tumors composed 
chiefly of the cement structure of the teeth. They are 
usually small growths resembling maxillary osteomata, and 
only on removal and microscopical examination will the 
structures characteristic of the cement substance be found. 

^Malassez and Galippe: Les Debris 6pith61iaux paradentaires, Paris, 
1910; Chibret: Arch, de m6d. exper. et d'anat. path., 1894, vi, 278; Kuru: 
Centralbl. f. allg. Path., 1911, xxii, 291; L'Esperance: Proc. New York 
Path. Soc, 1910, X, 136; Kaempfer: Surg-., Gynec, and Obst., 1911, xii, 
357; Bonney and Ellis: Surg., Gynec. and Obst., 1917, xxiv, 359. 

^Fischer: Frankfurt. Ztschr. f. Path., 1913, xii, 422. 

149 



They are benign tumors and quite infrequent. Occasion- 
ally, an odontoma is seen composed largely of connective 
tissue containing rudimentary teeth.^ Evidently both these 
types of odontoma, occurring usually rather early in life, 
fire due to malformations of the rudimentary tooth struc- 
tures, which do not reach normal development but undergo 
a tumor-like change, with irregular deposition of the vari- 
ous substances making up the normal tooth, as is shown 
by ^he fact that occasionally enamel is laid down in the 
growth of a mesoblastic odontoma. 

In addition to the tumors described, cysts derived from 
the tooth roots occur, one type beginning usually in the 
center of a granuloma formed at the site of a root and due 
to peridental inflammation. The cyst may be lined by epi- 
thelium, and giant cells also may be present. Such cysts 
may grow to an enormous size and extend into the antrum. 
The other type, the dentigerous cyst, arises from the over- 
growth of the follicle of a non-erupted tooth. According to 
the embryonic stage at which this cyst began to form, 
there will be found in it a more or less well developed tooth 
with the crown lying in the interior or in the wall, and the 
lining may show adamantine epithelium; but usually there 
is only granulation tissue owing to the early infection of 
the contents of the cyst. The cyst may fill up with debris, 
desquamated epithelial cells, and cholesterin crystals; and 
calcification may take place. Occasionally, the cystic pro- 
cess extends to the entire ramus of the jaw and converts 
it into a spongy mass of communicating or separated thin- 
walled cystic cavities, best revealed by x-ray photographs. 
In this case there may be no external cyst protruding from 
the ramus, but the outline of the superior maxilla may be 
so altered as to call attention to the condition.^ 

iSchlossman: Zieglers Beitr., 1908, xliv, 311. 

so altered as to call attention to the condition.^ 

of the Jaws, Philadelphia, 1912. 

150 



CHOLESTEATOMA 

Under this heading are classified a series of cystic or 
solid tumors with shining, white, pasty contents and a thin 
epithelial covering, which are of rather obscure origin, 
many unquestionably being due to congenital displacement 
of epidermal cells, others to chronic inflammatory pro- 
cesses. These rare tumors occur most frequently in the 
middle ear and brain. In the latter situation they are 
usually inside the pia mater, lying on the surface of the 
brain near the middle line, though rarely they may involve 
the ventricles; in any case they are not surrounded by 
brain substance. A few tumors of this variety have been 
seen in other regions of the body, for example, the floor of 
the mouth, the orbit, the genitourinary apparatus,^ and the 
sacral region. They are probably derived from the displace- 
ment of epithelial cells without any of the normal elements 
of the fully developed skin being carried with the cells.^ The 
tumors of the ear are probably derived from the fetal dis- 
placement of epidermis during the closure of the first 
branchial cleft, or from an ingrowing of the squamous epi- 
thelium of the external auditory canal following some de- 
fect or perforation of the ear drum.^ 

Macroscopically, the cholesteatomata are thin-walled 
tumors with shining, soft, wax-like contents. The material 
is often arranged in concentric plates of a whitish or 
mother-of-pearl color. Hair has been found in one case 
from the meninges.* 

Microscopically, the wall is composed of a thin layer 

^Biichanow: Cholesteatombildung in der Harnblase, Prag. med. 
Wchnschr., 1898, p. 525; Coenen: Cholesteatom des Nabels, Beitr. z. klin. 
Chir., 1908, Iviii, 718. Unterberger: Cholesteatom des Schadelknochen, 
Deutsch. Ztschr. f. Chir., 1906, Ixxxi, 90 (bibl.) 

^Bostroem: Centralbl. f. allg-. Path., 1897, viii, 1 (bibl.). 

^See for further details concerning' this particular type of choles- 
teatoma, Haug: Centralbl. f. allg. Path., 1895, vi, 124. 

^Bonorden, M.: Zieglers Beitr., 1892, xi, 593. 

151 



of epithelial cells, usually not more than three or four cells 
in thickness. The contents is a mixture of cholesterin 
crystals and flattened epithelial scales with more or less 
sebaceous matter and debris. Occasionally the flat rhombic 
plates of the cholesterin lie in tissue spaces bounded by 
giant cells. Some calcification of the contents is not in- 
frequent. 

The tumors are quite benign in their clinical course 
and are usually accidentally found. When tumors of large 
size occur in the brain they may cause death by inducing 
hydrocephalus from pressure ; in the orbit and facial sinuses 
they may erode the bone; in the middle ear they usually 
incite a chronic otitis media. 

The diagnosis may be made, as a rule, by simple in- 
spection of the incised mass. Microscopical examination of 
the wall and of the cyst contents will render the diagnosis 
positive, but it must be remembered that a lining of 
squamous epithelium is a prerequisite to a diagnosis of 
cholesteatoma, as distinguished from the mere retention 
cysts filled with debris, fat, and cholesterin, such as are 
not infrequent in the cystadenomata of the mammary 
gland. 

ADENOMA 

An adenoma is a tumor arising in a gland and preserv- 
ing in its structure some of the more important relation- 
ships which normally exist between the glandular epithe- 
lium and its supporting connective tissue. They are an ex- 
tremely frequent and clinically important group of tumors 
which may occur either as nodules in the substance of solid 
glandular organs or as polypoid masses projecting from 
the surface of a mucous membrane. In the skin, adenomata 
are derived from the sweat or sebaceous glands. They are 

152 



common in the thyroid, and fairly frequent in the liver, 
kidney, prostate, and adrenals, but are rarely seen in some 
of the glands, such as the pituitary. The most common 
sites are the ovary and the breast in the female. The poly- 
poid form is most frequent in the gastrointestinal tract and 
in the uterus, and is of great importance, as malignant 
changes are especially liable to occur in them. The adeno- 
myomata of the latter organ will be considered in another 
place. 

The polypoid adenomata of the gastrointestinal tract 
and uterus are composed of long, narrow, or cystic glands, 
usually larger than the normal structures, inclosed in a 
loose stroma which regularly shows the effect of inflam- 
matory lesions, because of the poor nutrition of the tissues 
and the traumatic insults which it is liable to receive from 
contraction of the viscus upon the tissue. A basement 
membrane upon which the gland cells are arranged, sur- 
rounds each tubule. In the intestine, the polyps may reach 
such a size that they obstruct the lumen of the gut or 
cause serious disturbance by induction of intussusception. 
They are often the site of carcinomatous changes. The 
microscopic determination of this fact requires great care, 
because the specimen removed for diagnosis rarely includes 
the base of the polyp, and, therefore, no evidence of in- 
vasion of the tissues of the intestinal wall can be obtained 
from the examination. Often the carcinomatous change in 
the gland cells is sufficiently characteristic to make a posi- 
tive diagnosis on the morphology alone ; but when it is not 
the report should always include a statement of the fact 
that other portions of the growth not submitted for ex- 
amination may be malignant. 

The adenomatous polyps of the uterus and cervix are 
much more often of a benign nature, but occasionally a 
polyp is carcinomatous, or a myosarcoma will be found of 

153 



polypoid form, and some of these tumors show evidence 
of malignant qualities in the glandular structures. 

Adenomata of the kidney and liver are unimportant 
from a clinical standpoint, as they are usually found only 
accidentally in operative material or post-mortem, and do 
not necessarily exert any influence on the well being of the 
patient. Liver adenomata usually occur in connection with 
cirrhosis, and, as is well known, cirrhotic livers are also a 
favorite site for carcinomatous change. 

Among the most interesting types of the adenomata 
are those tumors occurring in the thyroid gland, arising 
either in normal or in goiterous glands. When cut across, 
the adenomatous portions are seen to be distinctly outlined 
from the rest of the gland, and, usually, are much firmer to 
the touch and have a distinctly different color, being paler 
than the colloid-containing material of the goiter. The 
amount of true thyroid colloid in the tissues of the adeno- 
matous portions of the tumor is quite variable ; the earlier 
smaller growths contain very little and are mainly made 
up of compact combinations of alveoli. The older and larger 
adenomata, however, frequently contain a very consider- 
able amount of colloid material. 

These adenomata are generally held to arise in por- 
tions of the gland which have been left during embryonic 
development and are, therefore, separated in an anatomical 
and functional way from the rest of the organ. They have 
been found, also, in accessory thyroids. There is no evi- 
dence that they tend to become malignant, that is, undergo 
a change to true carcinoma of the thyroid; but, in rare 
instances, metastases may take place.^ These metastases 
are of the same structure as the original adenoma and 
show characteristic alveoli filled with the specific secretion 

^Gierke: Virchows Archiv, 1902, clxx, 363; Oderfeld and Steinhaus: 
Centralbl. f. allg. Path., 1901, xii, 209; 1903, xiv, 84; de Crignis, R.: 
Frankfurt. Ztschr. f. Path., 1913, xiv, 88. 

154 



of the thyroid gland. The tissue contains iodine also. The 
metastatic tumors occur with especial frequency in the 
skeletal system and often give rise to spontaneous frac- 
tures of the bone.^ The thyroid tissue forms discrete, firm 
nodules, and on microscopic examination it is strikingly 
like the original from which it was derived. The tumors 
remain fairly sharply outlined and do not, as a rule, grow 
in infiltrative fashion through the tissues in which they 
occur. For this reason Ribbert believes, in contrast to 
Gierke, that they are still true adenomata and not carci- 
nomata. The latter assumes that in order to metastasize 
the tumor must have changed and become a carcinoma, in 
other words, must have undergone a real biological change 
before metastasis could occur. Ribbert, on the other hand, 
holds that there is no reason why, if mechanical oppor- 
tunity is given for the cells to enter the circulation, metas- 
tasis of normal tissue should not take place, inasmuch as 
thyroid has been transplanted artificially.^ The fact that 
metastases are more frequently found in the bone has led 
to the assumption that the bone marrow offers a good soil 
for the growth of the thyroid tissue. Experimental work 
on animals has shown, however, that the subcutaneous 
tissue is a much better site for implantation than bone 
marrow, and the frequency of metastasis is probably due 
rather to the fact that the cells are few in number when 
they escape from the thyroid adenoma, pass through the 
capillaries of the lung, and find a quiet resting place in the 
marrow, where they grow undisturbed by mechanical 
effects. Metastatic tumors have, indeed, been found in 
the lung; but unquestionably the expansion and contrac- 
tion of the lung tissue with inspiration make it much more 
difficult for the cells to take a foothold in the capillaries, 

iKanoky: Surg., Gynec, and Obst., 1916, xxii, 679 (bibl.). 
*Manley and Marine: Jour. Am. Med. Assn., 1916, Ixvii, 2'60. 

155 



and, hence, metastases are more frequent in the bone mar- 
row than in the lung. 

The tumors which are found about the root of the 
tongue and along the course of the thyroglossal duct, and 
are composed of thyroid tissue, are not to be classed as 
adenomata, but rather as hyperplastic rudiments of the 
thyroid left during fetal development, though, if the thyroid 
atrophies, they may function.^ 

Adenomata of the breast are am.ong the important and 
most frequent tumors of that organ. They are usually to 
be called fibroadenomata on account of the abundant and 
dense stroma which they possess. In general, they are 
benign tumors, lobulated, well encapsulated, and freely 
movable in the substance of the organ, and may be single 
or multiple. Pure adenoma is exceedingly rare.^ Micro- 
scopically, they are composed of dense connective tissue 
surrounding areas of more or less atrophied glandular 
structures, the epithelial cells of which show no tendency 
to escape from the confines of the basement membrane. 
Usually there is some small-cell infiltration between the 
gland tubules. The connective tissue is very firm, and con- 
tains but few vessels and very few wandering cells. In- 
tracanalicular fibroadenoma is another type in which the 
gland structures dilate and papillary projections of soft 
mucoid connective tissue protrude into the lumen, filling it 
completely. These papillary ingrowths are covered with 
epithelium which is often single, but may be composed of 
several layers. In another type the connective tissue sur- 
rounds the glands, the so-called pericanalicular fibroade- 
noma. This is a rather infrequent form, the intracanalicular 

^For details concerning these tongue tumors, see Ungermann: Vir- 
chows Archiv, 1907, clxxxvii, 58; Wood: Proc. New York Path. Soc, 1916, 
xvi, 84; Mayo: Jour. Am. Med. Assn., 1911, Ivii, 784; and Erdheim: 
Zieglers Beitrage, 1904, xxxv, 366; Zuckermann, H,: Frankfurt, Ztschr. 
f. Path., 1913, xiv, 126. 

2Kuru: Deutsch. Ztschr. f. Chir., 1909, xcviii, 415. 

156 



being much more common. In the past it was often thought 
that the intracanahcular fibroadenomata underwent sarco- 
matous change, but the present view is that such tumors 
have been sarcomatous from the beginning, and that an 
alteration of a benign tumor of this type into a malignant 
one is exceedingly rare.^ Another and most important form 
of adenoma of the breast is the cystadenoma (Schimmel- 
busch), also designated chronic cirrhosing mastitis (Bill- 
roth), chronic interstitial mastitis (Bryant), cystic disease 
of the breast (Reclus), and chronic cystic mastitis 
(Konig).^ This variety in nomenclature is due largely to 
the fact that the lesion varies greatly in different examples 
and may show an excessive amount of inflammation in one 
instance, and a large overgrowth of epithelium or cyst 
formation in another. A third variety of lesion occurs. 
The whole breast may be converted into cysts, some of them 
filled with clear fluid, some with a chocolate-brown viscid 
substance due to hemorrhage, others with a butter-like 
solid mass, due to retention and inspissation of milk. These 
cysts are formed of dilated glands and ducts in which the 
various substances have collected. Areas of inflammation 
are apt to occur about these cysts with foreign-body giant 
cells, especially where there has been much collection of 
fatty material or cholesterin. In another type, the glands 
remain small and are filled with proliferating cells. Sur- 
rounding such gland tubules the connective tissue may be 
very cellular and give rise to the suspicion of a sarcoma 
or of a carcinoma, the epithelium penetrating the basement 
membrane and thus escaping from the alveoli. The tumors 
may be largely cystic, with the cysts filled with papillary 
ingrowths or solidly plugged with cells which resemble 

iSpeese: Ann. Surg., 1910, li, 212; Prym: Frankfurt. Ztschr. f. Path., 
1912, X, 60. 

^Greenough and Hartwell: Jour. Med. Research, 1903, N. S. iv, 416 
(bibl.); Berka: Zieglers Beitr., 1912, liii, 284 (bibl.). 

157 



very much those of a carcinoma. In other alveoli the filling 
cells may be of the colostrum type with small nuclei and 
large vesicular cell bodies, in which by suitable stains the 
fatty material can be demonstrated. Two other interesting 
conditions involve the breast. One is the occurrence of 
dilated glands of the type of the sweat glands; another, 
rarely seen, is the presence in the tumor of glands lined 
by flattened squamous epithelium.^ Finally, into the dilated 
glands of one of these tumors may grow various types of 
papillary projections springing from the wall. This is 
especially common in the excretory ducts leading to the 
nipple, but may occur deep in the substance of the breast 
itself. Such growths are to be regarded with considerable 
suspicion, since they frequently give rise to carcinoma, as 
will be found by a careful study of the base of the papillary 
outgrowth, where epithelial penetration of the connective 
tissue may be discovered. A complete description of the 
gross morphology of the cystadenomata of the breast is 
impossible because no two tumors are exactly alike. Ob- 
viously, they are not encapsulated ; they form rough, grainy, 
cystic masses often involving both breasts. In them carci- 
noma may arise. Whether this change is an alteration of 
the tumor itself into the neoplasm under conditions of 
chronic irritation, or whether the neoplasm springs of it- 
self from gland structures and is independent of the cysta- 
denomatous process is still not cleared up. It is certain that 
in the majority of cases of carcinoma extensive cystade- 
nomatous alterations are not present in the rest of the 
breast, and in tumors which are predominantly cystade- 
nomatous only about 10 per cent, show carcinoma. 

The diagnosis of cystadenoma is often possible from 
the gross appearance of the tumor. The only question which 
arises is whether a complete operation is necessary, that 

HJroh^: Deutsch. Ztschr. f. Chir., 1900, Iv, 67. 

158 



is, excision of the axillary lymph-nodes and the pectoral 
muscles and their fascia, or whether excision of the breast 
is sufficient. If the tumor is not malignant, the latter is, 
of course, the process which should be selected ; but the de- 
termination of the malignancy or benignancy of these 
tumors is sometimes extremely difficult. Many sections 
have to be examined from all portions of the growth and 
careful studies made of the relation of the epithelium to 
the connective tissue between the cysts. If this connective 
tissue contains unquestionable epithelial cells, the tumor 
must be assumed to be malignant; but unless this occurs, 
and if the cells are still confined within a well marked base- 
ment membrane, the tumor is benign. I have seen tumors, 
however, in which no evidence of carcinoma could be de- 
tected, but in which there was neoplastic invasion of the 
axillary nodes. In view of such a possibility and of the 
frequent occurrence of carcinoma in these tumors, they 
should all be removed by operation as soon as the diagnosis 
has been made, especially as most of them occur in the 
breast at a period when that organ has ceased to be func- 
tionally useful. 

The cystadenomata of the ovary form an important 
group of tumors. They can be divided into two types, the 
pseudomucinous cystadenoma and the serous or papillary 
cystadenoma. The first form is composed of larger or 
smaller cysts, the separating walls of which may ultimately 
break down so that the daughter cysts communicate with 
each other and form one large cavity involving the whole 
ovary. The contents are a thick, viscous, ropy fluid, or a 
jelly-like mass usually colored somewhat by blood pigment. 
The walls of the individual cysts are composed of fibrous 
tissue of fairly dense quality and are lined by epithelium. 
This epithelium is high and cylindrical in type and fre- 
quently assumes the form of beaker cells owing to the ac- 
cumulation of mucinous material within the cell itself. Very 

159 



frequently, however, the cells owing to pressure become 
flattened and atrophied, and may desquamate; but there is 
usually a more solid portion of the ovary, in which the pro- 
cess is still in its inception, which will show the high 
cylindrical type of cell and permit a diagnosis. Chemically, 
the cyst contents include the substance known as pseudo- 
mucin, which contains a carbohydrate radicle which can 
be split off by boiling the fluid with an acid, after which 
reduction tests can be obtained. In addition, there is much 
debris of various sorts. Usually there are numerous de- 
generating or fatty cells from the cyst lining mixed with 
red and white corpuscles, also much free fat, cholesterin 
crystals, pigment granules of various types, hematin, and 
other residues of the degenerated tissues. Suppurative in- 
flammation is not uncommon. The cysts may perforate into 
the peritoneum, bladder, vagina, or rectum. They may 
become gangrenous or hemorrhagic, especially after torsion 
of the pedicle. In rare instances, carcinoma develops. This 
type of tumor is one of the most frequent of those found 
in the ovary, forming more than half of the tumors of that 
organ. It is bilateral in not more than 20 per cent, of the 
cases. When the cystic mass ruptures, either spontane- 
ously or during an operation, the epithelium may grow 
on the peritoneal surface and form the so-called pseudo- 
myxoma peritonei. This is a diffuse sluggish growth of the 
characteristic cylindrical cells of the tumor, which excrete 
a jelly-like material, resembling that of the original cyst 
contents, and containing columnar cells and pseudo-mucin. 
The abdomen may be enormously distended, and death may 
result from malnutrition or intestinal obstruction. On the 
other hand, in cases when the abdominal cavity has been 
opened and the mucoid material removed as far as possible, 
repair has been noted with permanent cure. 

160 



The papillary cystadenomata are of a somewhat dif- 
ferent type. They are characterized by a papillary out- 
growth of cauliflower-like tufts, which springs from the 
walls of the cyst. They often break through the capsule, 
and appear on the surface of the ovary. The tumors are 
apt to be much smaller than the previously described type 
and contain a thin watery fluid. The cells covering the 
papillae and lining the cyst walls are usually cubical or 
columnar and sometimes ciliated. As a rule, they are 
present in a single layer. Malignant changes are much 
more frequent in the serous type of cyst than in the 
pseudomucinous form, and most of those in which papillae 
appear on the surface of the ovaries must be considered 
as malignant. Recurrences after removal appear in about 
75 per cent, of the cases. Ascites is present as a rule, and 
secondary peritoneal implantations at the time of operation 
are not infrequent. Such implantations are less apt to 
disappear after the removal of the tumor than in the 
pseudomucinous type. On the other hand, a few instances 
have been observed in which although diffuse involvement 
of the peritoneal surface was noted at the time of operation, 
the patient remained permanently well. 

Diagnosis of either of these types of tumors can be 
made by inspection. The only point to be decided is whether 
they must be considered as malignant or benign. This may 
require a very careful search of a large amount of material, 
and often the history and clinical appearance at the time of 
operation are of great value. If peritoneal metastases 
already exist at that time it is very probable that the 
tumor is malignant. 

The histologic origin of the cystadenomata of the 
ovary has been the subject of much discussion, and is not 
yet fully settled. They are usually assumed to be derived 
from solid or tubular ingrowths of the superficial germinal 
epithelium, and not from the Graafian follicles nor the 

161 



Pfliiger's cords, which are ingrowths of peritoneal epi- 
thelial cells. From their morphology, some of them have 
been suspected of arising from the ducts of the parovarium. 
Ribbert, however, holds that they may be portions of an 
only partially developed teratoma, and points out the re- 
semblance of the cells of the pseudomucinous type to those 
of the intestine. Some color is given to this suggestion 
by the fact that pseudomucinous cysts and teratoma of 
the ovary not infrequently occur together. 

CARCINOMA 

A carcinoma is a malignant tumor of epithelial origin. 
As this is a biological classification, and not a morphological 
one, we may expect in the tumors so grouped to find tran- 
sitions from purely normal gland structures with abundant 
stroma into growths composed largely of epithelial cells, 
for malignancy is not determined necessarily by the mor- 
phology of a tumor. In some instances, a growth appar- 
ently malignant proves to be benign; and in others, a 
growth apparently benign may be malignant, so that the 
only final criterion of malignancy is the behavior of the 
tumor in the body of the host. This fact is important to 
remember in the microscopic study of tumors of this group, 
which are often confusing because of the great variety in 
the structures which they contain, and because of a ten- 
dency which seems ineradicable to think that there must 
be something characteristic about the tumor cell; whereas 
the cell itself is not in the least different from cells of 
similar origin undergoing division at a rate comparable to 
that which takes place in the tumor cell. It should be re- 
membered in the determination of the biological qualities 
of a growth that a survey of its topography is much more 
important than the minute study of each individual cell; 

162 



and for this reason much routine diagnosis can be done 
with the low power of the microscope. It is true, also, that 
the morphology of the cell and habit of growth is, under 
normal circumstances, largely dependent on the physical 
condition in which the cell finds itself in the various organs 
of the body, as well as upon the duties which it has to 
perform. A cell on the surface of the skin has but little 
to do except resist traumatic influences, and to become 
ultimately comified and finally discarded. The same cell, 
growing into a mass of granulation tissue where the sources 
of nourishment are infinitely greater than in the normal 
situation, and where there are no restraining mechanical 
factors which prevent its developing, may assume the most 
bizarre shape, send out long processes, and be, as a matter 
of fact, indistinguishable from a connective-tissue cell. The 
careless thinker immediately assumes a metaplasia from 
epithelium to connective tissue. In this connection much 
concerning the peculiar conditions which mold the mor- 
phology of the cell has been learned from tissue cultures, 
in which connective tissue or epithelium is to a certain ex- 
tent free from mechanical restraint. The curious shapes 
which cells assume under these circumstances are interest- 
ing as showing how important are the normal conditions 
of organic relationship in the modelling of the cell. An- 
other source of confusion in the examination of malignant 
epithelial tumors is the extraordinary variety of degenera- 
tive and inflammatory processes which go on simultaneously 
with the growth of the neoplasm. Ulceration may give en- 
trance to bacteria, and these set up a suppurative inflam- 
mation with toxin absorption which involves the tumor 
cells as well as the normal, and often induces hyperplastic 
changes in the sinuses of the neighboring lymph-nodes. The 
presence of such irritative lesions has repeatedly led to the 
erroneous diagnosis of metastatic carcinoma. Hemorrhage 

163 



into the stroma of a malignant epithelial tumor is not in- 
frequent. If the blood remains in the tissue it may be more 
or less completely absorbed, or may leave yellowish masses 
of hemosiderin in various places. This may set up inflam- 
matory irritative reaction with production of giant cells. 
Similarly in the breast the escape of inspissated milk and 
subsequent alteration of the fatty material from the 
secreting glands seem to give rise to irritating substances 
which incite extensive chronic inflammation and the for- 
mation of a richly cellular tissue containing many giant 
cells inclosing fatty acid crystals or cholesterol. Carcino- 
mata are particularly liable to chronic degeneration of the 
connective tissue, of a fatty, mucous, gelatinous, or amyloid 
type, and these must all be allowed for in the study of the 
individual case. The carcinomata during the course of 
their growth encroach upon the adjacent tissues, and bring 
about a certain amount of destruction, either by pressure 
atrophy or by metabolic processes. As there has been no 
demonstration of a toxin from cancer cells and as the fer- 
ments of the cells have no powers to kill normal healthy 
cells, the only justifiable assumption is that the metabolism 
of the rapidly dividing cancer cell furnishes products which 
have a slightly irritating effect on the tissue, and may 
cause either a small amount of necrosis or may stimulate 
the cells of the neighborhood to increased proliferation. 
This is quite constantly seen, and the mitoses in the neigh- 
boring connective tissue and the evidences of rapid growth 
have led to the erroneous assumption that the carcinoma 
was giving rise to a sarcoma. That this change may occur 
in rare instances is probable, but only under peculiar cir- 
cumstances, and in an infinitesimally small number of cases 
as compared to the number of carcinomata which grow 
without in any way inducing such changes. Tumors so 
produced, the carcinosarcomata, will be discussed in another 
paragraph. The older view, also, that the cells of a tumor 

164 



were able to influence in some fashion the neighboring 
cells of the same type so that the cancer spread by waves 
through cells altered so as to assume malignant qualities 
under the influence of the central primary portion, is now 
no longer accepted, the prevailing belief being that most 
neoplasms start from a group of cells, small in number, or 
even from a single cell, and that all successive generations 
are descendants of this original organism. 

Types of Carcinoma 

The cells of certain forms of carcinomata of the skin 
and mucous membrane have the same morphology as the 
epithelium from which they arise, and so have been 
designated squamous-cell or flat-cell epitheliomata. In an- 
other form, which frequently attacks the gastrointestinal 
tract and the uterus, the cells are more or less cylindrical 
in shape, and, therefore, the neoplasms which arise from 
them have been designated cylindrical-cell carcinoma. A 
type which contains an abundance of blood-vessels is called 
carcinoma telangiectoides. Other types are epidermal car- 
cinoma and glandular carcinoma. Other names, mostly in- 
herited from the older days of descriptive morphology, are 
medullary or encephaloid carcinomata, or carcinoma molle, 
by which is designated a tumor which is soft and composed 
largely of parenchyma cells with but little connective 
tissue. Tumors containing approximately equal amounts 
of parenchyma and stroma are called carcinoma simplex, 
while one in which the stroma preponderates is known as a 
scirrhous carcinoma, or ''scirrhus." There is no constant 
biological difference between any of these tumors. A med- 
ullary carcinoma composed of large cells may be much 
more benign than a highly scirrhous tumor composed of 

165 



small cells which may pass into the lymphatics and blood- 
vessels with greater ease than the larger cells of the more 
richly cellular tumor. A common fallacy in wide circula- 
tion among pathologists is that connective tissue chokes 
cancer cells and destroys them. There is not the slightest 
evidence that one tissue of the body has any capacity 
directly to destroy another, and the kernel of truth which 
is contained in this as in many other inaccurate statements 
is that in the densely fibrous tumors less nourishment is 
afforded to the cancer cells and they remain more or less 
quiescent, until they escape into some channel where food 
is more available. Thus a scirrhous carcinoma may remain 
fairly quiescent for some years and grow very slowly, so 
that the assumption might be made that it was held back 
by the connective tissue, but usually in such a case wide- 
spread involvement of the lymph-nodes can be found even 
when the tumor itself is extremely small. Thus, this type 
is more malignant to the host than a form which announces 
its nature earlier. 

Among other varieties which have not been mentioned 
are those carcinomata which depend for their characteris- 
tics upon degeneration or metamorphic products which 
the cells contain. These are gelatinous carcinoma and 
melanocarcinoma. That function does not interfere with 
malignancy is seen from the fact that while the gelatinous 
carcinomata, on account of the close adhesion of the cells 
one to another, are fairly benign, the melanocarcinomata, 
in which the cells produce melanotic pigment, are among 
the most malignant that we know. In general, the present 
day tendency is to neglect the use of the older descriptive 
names and to classify those arising from the skin as epi- 
theliomata, subdividing the group into basal-cell or 
squamous-cell, because this is important from a practical 
point of view, as showing the difference in biological nature. 

166 



The tumors arising from glandular epithelium are desig- 
nated carcinoma. We still speak of glandular carcinomata, 
or adenocarcinoma, and the adjective "scirrhous" is still 
retained as a useful descriptive term. Gelatinous carcino- 
mata should be so designated, because of their very con- 
siderable relative benignancy; and if melanotic pigment is 
present, attention should be called to this fact as indicating 
a high degree of malignancy in the tumor. Only those 
descriptions which have useful clinical connotation are 
widely employed at the present time. 

» 
Epithelioma 

An epithelioma is a malignant tumor whose charac- 
teristic cells are derived from the epithelium of the skin 
or the mucous membranes. While, in a general w^y, it 
may be stated that epithelial tumors containing cells of 
the squamous type are confined to regions covered by flat- 
tened epithelium, such as the skin and the mucous mem- 
branes, yet occasionally tumors containing typical squam- 
ous epithelium with spines and fibrillations may be found 
in surfaces whose cells are derived not from the epiderm 
but from the entoderm. Such heterologous epitheliomata 
appear in the bronchi,^ stomach, large intestine, pancreas, 
prostate, endometrium, mammary gland,^ pelvis of the kid- 
ney, urinary bladder, and thyroid and salivary glands. The 
tumors of the skin, however, form the vast majority of 
true epithelial tumors. They are of two types, basal-cell 
and squamous-cell. 

iHerxheimer: Uber heterolog-e Cancroide. Zieglers Beitr., 1907, xli, 
348. 

^Griffiths: Fibrocystic Tumor of the Breast, in -which the Majority 
of the Cysts are lined by Stratified Epidermis-like cells. Jour. Path, 
and Bacteriol., 1901, vii, 447. 

167 



The appearance of the basal-cell epitheliomata is fre- 
quently preceded by a benign thickening of the epidermis 
known as seborrheic keratosis. These are round or oval 
brownish papules which occur chiefly on the skin of the 
face and form when fully developed flat-topped elevations 
of yellowish or brownish color which are usually circum- 
scribed, covered with a firmly adherent, greasy, velvety 
crust. Microscopically, the horny layer of the skin is thick- 
ened; the papillae are enlarged and elongated. There are 
usually chronic inflammatory lesions of the hair follicles 
and the sweat glands, and in the corium there is apt to be 
a considerable cellular infiltration, composed chiefly of 
lymphocytes and plasma cells. Such seborrhoic keratoses 
may exist for a long period without any change taking 
place in them, but ultimately in a certain number the 
growth changes its characteristics, becomes more elevated, 
may ulcerate, be covered with a crust, and then if excised 
will be found to show the lesion of an epithelioma, usually 
of the basal-cell type.^ The basal-cell epitheliomata are 
slow-growing tumors which may spread over the skin for a 
considerable distance and even show evidence of healing 
in one portion while extending in another. They are a very 
common type of tumors, and are seen chiefly about the 
face, near the angles of the nose, on the eyelids and ears, 
and, as a rule, above the upper lip. They almost never 
form metastases. 2 

Microscopically, the tumors are composed of masses 
of epithelium lying beneath the skin and of a different type 
from the squamous epithelium of the surface. Whether the 
tumors all originate in the basal layer of the skin, as has 

iSutton: The Symptomatology of Seborrheic Keratoses, Jour, Am. 
Med. Assn., 1915, Ixiv, 403. 

^See, however, Montgomery: A Case of Epithelioma with Infection 
of the Lymph Nodes, Ann. Surg., 1898, xxvii, 193. 

168 



been claimed by Krompecher and others/ or whether some 
of them begin in the cells of the hair follicles, sebaceous 
glands, or other structures, of the developing skin is still 
undecided. The weight of opinion, however, favors the view 
that these tumors come from the basal layer of the skin. 
The cells are small, deeply staining, with small nuclei, and 
lie either in compact masses or in gland-like arrangements, 
the alveoli of which may be filled with mucoid material. 
In a small proportion of tumors areas of prickle cells show- 
ing cornification and intercellular bridges may be found. 
Barber^ found that 7 per cent, of basal-cell tumors contained 
epithelial pearls. These tumors are more malignant than 
the purely basal-cell types. 

In some instances, the epithelium has no connection' 
with the superficial layers, and hence has been supposed to 
originate from epithelial remnants. Tumors of this mor- 
phology have been called ''corium carcinoma."^ 

The diagnosis is often possible clinically. A very slow- 
growing tumor which has been evident for some years in 
the skin of an old person can hardly be anything else than 
a basal-cell epithelioma. Beginning tumors are more diffi- 
cult to diagnose. As a rule, the edge of the tumor is pearly, 
and, if ulcerated, tends to form a crater-like border around 
the excavated area. There is but little tendency to pene- 
tration of the deeper tissues except in the later stages of 
the growth, when it may involve the bone or cartilage of 
the nose, or even penetrate the antra of the cheek. The 
eyelid tumors are almost always of the basal-cell variety, 
and in the later stages lead to destruction of the eye.* 

^Krompecher: Der Basalzellen Krebs. Jena, 1903, also Zieglers Beitr., 
1908, xliv, 51 and 88. 

^Barber, R. F.: Jour. Am. Med. Assn., 1915, Ixiv, 1790. 

•^Fisher: Epithelioma of the Lid, Jour. Am. Med. Assn., 1914, Iviii, 751; 

^Borrmann: Ztschr. f. Krebsforsch., 1904, ii, 1; 1906, iv, 91. 
for details concerning the topographical distribution of these tumors, see 
Broders: Basal-cell epithelioma, Jour. Am. Med. Assn., 1919, Ixxil, 
856; also Broders and MacCarty: Epithelioma, Surg., Gynec, and Obst., 
1918, xxvii, 141; Hazen: Jour. Am. Med. Assn., 1915, Ixvi, 958; Fordyce: 
Epithelial growths of the skin. Jour. Am. Med. Assn., 1910, Iv, 1624. 

169 



Microscopically, the basal-cell tumors can be determined 
at a glance. The characteristic cell masses do not resemble 
any other form of skin tumor. 

Squamous-cell carcinomata are tumors of very different 
type, both morphologicaly and biologically. They are highly 
malignant, metastasize very early to the regional lymph- 
nodes, and are among the most frequent tumors. At the 
beginning they may be either flat hard masses, or papillary. 
Usually the tumor ulcerates very early and the flattish ulcer 
is covered with a serous or sanguinolent fluid, or with a 
crust. While the basal-cell tumors are seen practically only 
in old people, the squamous-cell tumors are present in the 
earlier age groups. The writer has seen an epithelioma of 
the lip in a boy of thirteen. Like the basal-cell tumors they 
are most frequent about the nose, eyelids, lips, forehead, 
and temporal region. The back of the hand, especially in 
laborers, is a site where tumors may occur with fair fre- 
quency. They may arise in ulcers of all types, including 
the varicose ulcers of the leg, in sinuses, especially chronic 
bone sinuses, in ulcers of the tongue or cheek, in lupus, in 
scars of old burns, either from hot metal or from the 
x-ray, and, in general, where any chronic irritation of the 
skin or mucous membrane has occurred.^ 

Microscopically, the squamous-cell epitheliomata are 
formed of masses of squamous cells which in the earlier 
stages project down from the papillae of the skin only a 
short distance and are surrounded by the chronically in- 
flamed connective tissue, the infiltrating cells being lympho- 
cytes and plasma cells. The first evidence of malignancy 

iSee Heidingsfeld: The etiolog-ic role of scar tissue in skin cancer, 
Jour, Am. Med. Assn., 1916, Ixvii, 1499; also Hazen: Cutaneous cancer 
of the extremities; Jour. Am. Med. Assn., 1915, Ixv, 837 (bibl.). For 
epithelioma as a sequel to irritation, see Hartzell: Am. Jour. Med. Sc, 
1899, cxviii, 265; Schamberg: Cancer in tar workers, Jour. Cutan. Dis., 
1910, xxviii, 644; Sachs: Epithelioma-like warts from Aniline Dyes. 
TV^ien. klin. Wchnschr., 1911, xxiv, 1551; Engman: Precancerous Condi- 
tions of the Skin, Jour. Lab. and Clin. Med., 1915, i, 31. 

170 



is usually shown by mitoses in the basal layer with a fring- 
ing out of the epithelial cells into the inflamed serium. In 
the latter phases, when malignancy is beginning to be estab- 
lished, small areas of cells are to be found deeper in the 
tissues having grown from the papillae but still retaining 
their connection with it. In fact, serial sections have shown 
that isolated masses deep in the tissue are still mere out- 
growths of the superficial epithelium and only later when 
the cells penetrate the blood-vessels and lymph-channels do 
discrete metastases occur. When the disease is well ad- 
vanced, a considerable proportion of the corium is filled with 
epithelial cells, either in an active state of growth and divi- 
sion, or arranged in pearl-like masses which by their dif- 
ferent reactions to stains, taking a deep color with eosin, 
and by their morphology, show that cornification has oc- 
curred. While pearls can occasionally be found in benign 
papillomata, they are usually characteristic of the squam- 
ous-cell epithelioma. 

The early diagnosis of squamous-cell epithelioma is of 
the greatest importance owing to the highly malignant 
qualities of the tumor.^ While diagnosis can be made clin- 
ically in a large number of cases if sufficient care is taken, 
usually the microscope must be employed at the earliest 
possible moment, and to do this it is often necessary to 
remove a small fragment of tumor by a perfectly clear in- 
cision with a sharp scalpel. It is far better to do this and 
to run the risk of the somewhat hypothetical distribution 
of tumor cells throughout the body by opening of the blood- 
vessels or lymph-channels, than to delay a few weeks and 
permit the tumor automatically to spread itself throughout 
the body by the same routes. Clinically, the tumor is hard 
and cake-like, and can be picked up between the fingers 

'See for example Bloodgood: The surgical treatment of malignant 
growths, Jour. Am. Med. Assn., 1910, Iv, 1615; Carcinoma of the lower 
lip, diagnosis, and operative treatment, Surg., Gynec, and Obst., 1914, 
xviii, 404. 

171 



as a small disk even when very early in its growth. Chronic 
ulceration of the lip in a patient over forty-five should never 
be allowed to remain for more than a few weeks without 
definitive diagnosis. In advanced cases a firm, hard, spread- 
ing, irregular tumor with metastases to the lymph-nodes 
leaves no choice as to the diagnosis. 

Microscopically the diagnosis of the very earliest 
tumors is somewhat difficult. It may be necessary to cut 
the lesion into serial sections and examine every fifth or 
tenth section in order to be certain of the invasion of the 
corium by the cells of the papillae. In the later stages the 
diagnosis is perfectly simple, deep invasion by masses of 
epithelial cells with keratinized pearls being all that is 
necessary. If the lymph-nodes are invaded, the tumor is 
usually close to the operative limit. 

While the description in the text has been largely 
limited to the epitheliomata of the skin, because these are 
the most frequently occurring neoplasms, similar tumors 
appear in the cervix, vulva, and vaginal canal, at the anus, 
on the tongue and cheek, etc. 

Carcinoma 



For descriptive purposes the carcinomata may be 
divided into two groups, those arising from cylindrical epi- 
thelium and those from glandular. Of the forms arising 
from cylindrical epithelium the most important clinically 
are those of the stomach, rectum and uterus. Of the glan- 
dular carcinomata the most important are those of the 
breast, thyroid, liver and prostate. The epithelial cells of 
these two types of malignant neoplasms frequently preserve 
to a very great extent the structure of the glands from 
which they arise. 

172 



Cylindrical- Cell Carcinoma. 

Macroscopically, the tumors of the stomach are usually 
broad, flat, ulcerated masses involving most frequently the 
region of the pylorus and lesser curvature, extending into 
the muscularis and serous coats of the stomach, and in 
advanced cases invading the liver. In addition, the regional 
lymph-nodes are invaded, and the peritoneal cavity may 
contain some diffuse carcinosis. While this is the usual 
type of growth, there are several varieties which occasion- 
ally occur. One of these is a polypoid type, single or mul- 
tiple, in which the neoplasm has a more or less narrow 
pedicle and projects into the lumen of the stomach. An- 
other form is a diffuse scirrhous carcinoma completely in- 
volving the wall of the organ and converting it into a nar- 
row, bottle-like tube of great rigidity. The walls are, in 
addition, very fibrotic and may measure 2 to 3 cm. in thick- 
ness. There may be not the very slightest evidence of any 
ulceration or new growth of the mucous membrane, the 
whole tumor being confined to the muscularis and submu- 
cosa. In this type the small cells of the tumor do not as- 
sume glandular relationships, but are freely movable 
through the lymph-channels and blood-vessels, and, as may 
be expected, extensive lymphatic involvement or metastases 
in the liver are not uncommon. Because a tumor springs 
from cylindrical epithelium it does not necessarily retain 
the exact habit or form of the cells of its origin.^ 

The gelatinous carcinomata, also, in which large masses 
of mucoid material are secreted by the cancer cells, are 
found occasionally in the stomach. They are less malignant 

^The most important monographs on tumors of the stomach and in- 
testine are: Borrmann: Mag-encarcinoms, Mitt. a. d. Grenzgeb. d. Med. 
u. Chir., Erster Supplementband, Jena, 1910; Hauser: Das Cylinder- 
epithel-Carcinom d. Magens u. d. Dickdarms, Jena, 1910; Verse: Tiber d. 
Entstehung. d. Bau u. d. Wachstum d. Polypen, Adenome, u. Karzinome 
d. Magen-Darmkanals, Arb. a. d. path. Inst. z. Leipzig-, 1908, Erster 
Band. 

173 



than the scirrhous or alveolar types, but do metastasize. 
Squamous-cell carcinoma of the stomach also has been seen 
in a few instances.^ 

The tumors of the rectum involve the viscus either as 
cylindrical growths or as flat, limited masses invading only 
a portion of the wall. They are apt to be of the mucoid or 
gelatinous type, and only the smaller growths are of the 
pure adenocarcinomatous type. 

Carcinoma of the cervix and of the body of the uterus, 
also, may be of the glandular variety imitating either the 
cervical glands with their high cylindrical epithelium and 
basally placed nuclei or the glands of the endometrium. 
Tumors of the cervix are very malignant, and metastasize 
early into the broad ligament, while those of the body of 
the uterus frequently remain limited for a long period; 
hence, the operative results vary greatly. In some series of 
carcinoma of the body, 90 per cent, of cures have been ob- 
tained by excision of the uterus; whereas in carcinoma of 
the cervix, 20 per cent, is a good average. 

Microscopically, in the glandular carcinoma types, the 
tumors frequently retain many of the morphological char- 
acteristics of the structure from which they sprang. The 
basement membrane may be fairly well preserved, and the 
only differentiation possible between malignant and benign 
types is in a reduplication of the lining cells of the glands, 
or the occasional invasion by these glandular structures of 
positions where such glands never occur normally. For 
example, in early carcinoma of the stomach or rectum, the 
only evidence of malignancy may be the presence of a few 
glands deep in the muscularis or in the subserous coat. 
Even this is not absolute, for if an ulcer has been present 

iHerxheimer: Zieglers Beitr., 1907, xli, 348 (bibl.). 

174 



in the stomach wall for a long time, the glands on the peri- 
phery may grow into the deeper layers and give the mor- 
phological appearance of beginning carcinoma.^ In the later 
stages of a true tumor, on the other hand, the growth is 
generally formed of a mass of aberrant gland structures 
with but little resemblance to the normal. 

The gelatinous type is identifiable at a glance by the 
peculiar nature and appearance of the tumor. When it 
spreads into the peritoneal cavity, however, and fragments 
are removed for diagnosis without information as to the 
site of the primary growth, it is sometimes extremely diffi- 
cult to differentiate these from the pseudomyxoma peritonei 
following the rupture of an ovarian cystoma^ or mucoid 
disease of the appendix.^ The number of epithelial cells 
in the mucoid mass may be very small, and it is necessary 
to search with great care about the periphery of the tumor 
and in the firmer portions of the tissue removed, for lym- 
phatic spaces in which the characteristic cells of the glands 
of the stomach or intestine may be found. Here they form 
small signet-ring masses with the nucleus on one side and 
the cell body greatly distended by the mucoid secretion. 
These are the cells which have given the characteristic 
morphology to the so-called Krukenberg tumors of the 
ovary, which are usually secondary metastatic deposits from 
tumors of the gall-bladder or gastrointestinal tract. 

Glandular Carcinoma 

Carcinoma of the female breast offers an abundant and 
important example of the glandular type of carcinoma. The 
glands of the tumor may be so nearly normal that it is 

^Bullock and Rohdenburg-: Jour. Cancer Research, 1918, iii, 227. 

^McCrae and Coplin: Am. Jour. Med. Sc, 1916, cli, 475; Lewis: Surg., 
Gynec, and Obst., 1914, xix, 757. 

3Loth: Beit. z. klin. Chir., 1914, xciv, 47; Roth: Zieg-lers Beitr., 1916, 
Ixi. 42 (bibl.); Bailey, F. W.: Surg-., Gynec, and Obst., 1916, xxiii, 219. 

175 



difficult, and in some instances impossible, to tell whether 
the growth is an adenoma or a carcinoma; and the writer 
has seen one case in which only the metastases in the axil- 
lary nodes gave any clue to the malignant nature of the 
tumor. The glands may resemble perfectly those of the 
normal breast, or they may be dilated. While the epithe- 
lium is frequently in a single layer, it may occur in many 
layers, and often fills the entire lumen of the dilated gland, 
leaving only small spaces free for secretion. Two types of 
glandular structures may be seen in different parts of the 
breast in carcinoma, giving rise to two types of metastases 
as seen in the neighboring lym.ph-nodes, an evidence that 
biologically different types of carcinoma may arise simul- 
taneously in the same organ. The medullary form, also, is 
frequent in the breast, and presents no picture of special 
interest, except that large areas are filled with closely 
packed epithelial cells. The individual elements often show 
mitoses and spread out through the tissues and lymphatics 
to the axillary nodes. 

A third type very frequent in the breast is one in which 
a large amount of dense fibrous tissue forms the bulk of 
the tumor. Scattered through the connective tissue spaces 
there are a few, usually very small, carcinoma cells. The 
diagnosis in this instance may be difficult, if not impossible 
on gross inspection, and not easy on microscopic examina- 
tion. Here the involvement of the regional lymph-nodes 
may simplify the diagnosis. 

Other interesting examples of glandular carcinoma oc- 
cur, for example, in the thyroid, where the tumor may, as 
in the famous case of von Eiselsberg,^ furnish secretions 
which prevent the patient from suffering from myxedema. 

^Von Eiselsberg-; Ueber Physiologische Function einer im Sternum 
zur Entwickelung- gekommen krebsigen Schilddrusen Metastases. Arch, 
f. klin. Chir., 1894, xlviii, 489. 

176 



As this case has been frequently misquoted the following 
abstract may be of interest: 

The patient was a woman who had an enlarged thyroid 
since puberty. When she was twenty-nine years old the 
gland began to grow more rapidly and both lobes became 
enlarged and hard, with an especially hard nodule in the 
right and several smaller ones in the left lobe. She also suf- 
fered from dyspnea and tachycardia. 

Billroth extirpated the right lobe and then finding by a 
laryngoscopic examination that the trachea was still com- 
pressed, removed the left also. The patient left the hospital 
in good condition with only a slight irregularity of the pulse. 
Soon afterward she began to have spasms of the upper ex- 
tremities of the tetanic type, with fingers flexed in the char- 
acteristic position. In two months she became mentally 
dull, her face became swollen, and she suffered with cold. 
These symptoms were diagnosed as a severe degree of 
cachexia thyreopriva and a mild tetany. 

The next year a hard nodule developed in the upper part 
of the sternum and at the same time the mental state re- 
turned to normal and the swelling of the face disappeared. 
This condition remained for about two years at which time 
the sternal tumor began to grow rapidly. The patient 
showed no sign of tetany or cachexia, but the pulse was 
rapid. 

The manubrium and tumor were removed. The latter 
was found to be a cylindrical-cell carcinoma, with small drops 
of colloid throughout. 

Nine days after the operation tetanic spasms again ap- 
peared in both arms and hands. These improved for two 
weeks, then became very severe, but eventually improved 
again. The mental dullness returned the following year, 
but the face was not swollen. A tumor the size of a small 
orange finally appeared in the left scapula. 

177 



The morphology of these tumors follows that of the 
gland with the exception that the cells are much more 
abundant and the colloid material much less than under 
normal circumstances. 

Primary carcinomata of the liver are of two types, one 
springing from the liver cells, and the other from the bile 
ducts. Neither these nor the carcinomata of the pancreas, 
kidney, lung, or prostate are of sufficient morphological in- 
terest to warrant detailed discussion here. 

An interesting fact concerning carcinoma of the pros- 
tate is that nearly four-fifths of the tumors give rise to 
metastases in the osseous system, while similar tumors 
from other organs, with the exception of the thyroid, rarely 
form such early and extensive bone metastases. 

An interesting form of glandular carcinoma is the 
psammoma-carcinoma, which occurs in the ovary, the thy- 
roid gland, and the breast. In the ovary, it is the papillary 
type of carcinoma which shows the presence of the peculiar 
psammoma bodies, small calcified areas of the type referred 
to under the psammomata of the dura mater. The calcified 
areas may occur not only in the epithelial portion of the 
tumor, but also in the connective tissue of the ovary in 
the region of the epithelial portion of the neoplasm. In the 
uterus and thyroid the tumors are rare, and only a few have 
been described occurring in papillary adenocarcinomata of 
the glands. In the breast a considerable number of cases 
have been reported, chiefly in the very slow-growing, necros- 
ing carcinomata of old people. Giant cells may be found 
about areas of the necrotic and calcified cancer cells. A 
similar collection of giant cells is seen occasionally in the 
deeper layers of the epitheliomata of the face or the back 
of the hand in very old people, where the growth is soft 
and necrotic, or where cornified cells are set free in the 
connective tissue by necrosis of a portion of the growth. 

178 



That these giant cells take any active part in the destruc- 
tion of the epithelial cells is not to be considered ; they are 
only necrophages acting on cells after death, and do not 
attack living epithelium. 

Carcinoid Tumors 

The carcinomata of the gastrointestinal tract are con- 
fined largely to the stomach, caput coli, and rectum, and 
rarely occur in the small intestine and appendix. In these 
latter situations, however, there are seen tumors of a pecu- 
liar morphology,^ which in the appendix are fairly common, 
occurring in about 0.5 to 1. per cent, of all appendices re- 
moved; in the small intestine they are much rarer.^ The 
tumors are rarely diagnosticated during life, but are found 
in the course of routine operations from appendicitis or in 
the small intestine after death from some other cause. The 
benign character of these tumors, for only in a very few 
instances have they shown any malignant properties, and 
their peculiar morphology, have led to the opinion that they 
should not be considered as true carcinomata except in 
morphology, and to distinguish them from the highly malig- 
nant growths of the rest of the intestine they have been 
designated carcinoid tumors. They have been compared to 
basal-cell tumors of the skin.^ 

In the gross, these tumors form thickenings in the 
muscular layers of the intestine and are especially liable to 
occur at the tip of the appendix; the submucosa also may 
be invaded. The peritoneum is not involved. In the small 
intestine they are apt to form nodules a few millimeters in 

iRolleston and James: Am. Jour. Med. Sc, 1906, cxxxi, 951 (bibl.); 
Whipham: Lancet, 1901, i, 319; Moschcowitz: Ann. Surg., 1903, xxxvii, 
89 (bibl.); Vance: Proc. New York Path. Soc, 1916, xvi, 158 (bibl.). 

2Meyer: Surg-., Gynec, and Obst., 1915, xxi, 354 (bibl.). 

^Bunting: Bull. Johns Hopkins Hosp., 1904, xv, 389. 

179 



diameter, usually multiple, and lie in the submucous coat 
opposite the attachment of the mesentery. Usually they 
are sharply limited and are often encapsulated. 

Microscopically, the growth consists of small alveoli 
filled with lightly staining cells of uniform size with vesic- 
ular nuclei and only rarely mitotic figures. The cells lie 
closely packed together without connective tissue between 
the individuals. The diagnosis is based entirely on the micro- 
scopical appearances. 

Carcinosarcoma 

The observation that in animals mixed tumors contain- 
ing both carcinomatous and sarcomatous elements may oc- 
cur, or that sarcoma may apparently change into carcinoma, 
or the reverse, has led to a new interest in similar mixed 
tumors occurring in human beings. In mice the phenom- 
enon, which was first observed by Ehrlich,^ consists in 
the appearance of a sarcoma surrounding the alveoli of a 
carcinoma. In such a mixed tumor, the carcinoma or sar- 
coma may spontaneously outgrow the other element; for 
example, the Flexner-Jobling rat carcinoma was originally 
considered a sarcoma, but at the present time it is purely a 
carcinoma, and has been so through over 180 transplanta- 
tions during the past fifteen years. Certain transplantable 
carcinomata, also, have the power to induce sarcomatous al- 
terations in the stroma on transplantation to a new host, 
and it has been found that from one to three months' 
growth is required to produce this change. Whether the 
carcinosarcomata of man are explicable on this basis is not 

lEhrlich: Ztschr. f. Krebsforsch., 1907, v, 62; Apolant: KoUe and 
Wassermann, Handbuch d. path, Mikroorganismen, 2d ed., 1913, iii, 167. 
For a complete review of the cases up to 1913, see Wog-lom: Study of 
Experimental Cancer, New York, 1913; and Jour. Cancer Research, 1918, 
iii, 47. 

180 



certain. Apolant^ believes that the rarity of such secondary 
sarcoma formations in human beings is due to the fact that 
the original tumor leads to a rapidly fatal result, giving in- 
sufficient time to produce the transformation. It must, how- 
ever, be noted that certain pathologists^ believe that the 
sarcomatous fraction is an epithelial tumor in which the 
cells in certain areas have assumed a spindle shape. What- 
ever may be the result of the studies and discussion of the 
experimental material, the fact remains that there are a 
considerable number of human tumors in which both epithe- 
lium and connective tissue appear to take an active part in 
the growth. These tumors must be distinguished from 
those in which a carcinoma and a sarcoma have arisen 
separately in different portions of an organ and grown into 
each other; this is merely an example of multiple tumors. 
In the carcinosarcoma, the two types of growth must be 
together from the start. 

The carcinosarcomata seem to be especially abundant 
in the thyroid.^ The esophagus also is a frequent site.* 
Similar tumors have been seen in the breast and in the 
uterus.^ Unquestionably, some of these tumors are of tera- 
toid nature, as in addition to pure carcinoma and sarcoma, 
remnants of cartilage and myxomatous tissue have been 
demonstrable in some instances. This is the case with a 
complex tumor of the liver reported by Saltykow.^ Only 
about thirty of these tumors have so far been published, 
so that no definite gross appearances or clinical course can 

lApolant: Berl. klin, Wchnschr., 1912, xlix, 495. 

2Krompecher: Zleglers Beitr., 1905, xliv, 51, 88. 

3L.oeb: Am. Jour. Med. Sc, 1903, cxxv, 243 (bibl.) ; Wells: Jour, of 
Path, and Bacteriol., 1901, vii, 357; Saltykow: Centralbl. f. allg-. Path., 
1905, xvi, 547 (bibl.); Simmonds: Ztschr. f. Krebsforsch., 1913, xiii, 307. 

*Herxheimer: Verhandl. d. deutsch. path. Gesellsch., 1908, xii, 67; 
also Zieglers Beitr., 1908, xliv, 150; Herzog-: Verhandl. d. deutsch. path. 
Gesellsch., 1914, xvii, 346; Saltykow: ibid, 351. 

^Forssner: Arch. d. Gynec, 1909, Ixxxvii, 445. 

^Saltykow: Verhandl. d. deutsch. path. Gesellsch., 1914, xvii, 351. 

181 



be described, except that they combine the malignant quali- 
ties of carcinoma and sarcoma. The diagnosis is extremely 
difficult, and usually requires a careful study of consider- 
able portions of the tumor in order to determine the exact 
nature of the growth, though its malignant qualities can be 
recognized easily microscopically or even clinically. 

CHORIOMA (CHORIONEPITHELIOMA) 

Under the name chorioma^ are included tumors derived 
from the chorionic villi or from some abnormal form of 
these elements, such as hydatid moles. They are thus com- 
posed of cells more or less closely resembling those covering 
the chorionic villi, the connective tissue elements of the 
latter playing no part in the formation of the tumor. 

In order to understand the structure and biological 
characters of the tumors included in this group it is neces- 
sary to bear in mind the nature of the normal structures 
which go to make up the placenta. The chorionic villi con- 
sist of a loose, rather vascular connective-tissue framework 
containing much mucoid material, which is covered with two 
layers of epithelial cells of fetal origin,^ collectively desig- 
nated the trophoblast. The inner layer or cyto-trophoblast 
is formed, in general, of a single strand of sharply defined 
polyhedral cells with clear cell bodies and oval, deeply stain- 
ing nuclei. These cells contain considerable quantities of 
glycogen, and are usually called Langhans' cells. The outer 

iThe best review of the subject is by Teacher: Eden and Lockyer, 
A New System of Gynaecology, London, 1917, ii, 555. Most of the 
bibliography to 1907 is in Risel: Lubarsch-Ostertag;, Ergebn. d. allg. 
Path., 1907, xi2, 928. Other excellent papers are: Ewing: Surg., Gynec, 
and Obst., 1911, xi, 366; Hitschmann and Christofoletti: Wien, kiln. 
Wchnschr., 1911, xxiv, 655 and 705; Pollasson and Violet: Ann. de 
Gynec, 1913, Ixx, 257; Frank: N. Y. Med. Jour., 1906, Ixxxiii, 793; and 
Am. Jour. Obst., 1911, Ixiv, 435. 

^Marchand: Monatschr. f. Geburtsh. u. Gynak., 1895, i, 419; also 
Ztschr. f. Geburtsh. u. Gynak., 1895, xxxii, 405; 1898, xxxix, 173. 

182 



layer, or plasmodio-trophoblast, is composed of a protoplas- 
mic mass with no distinct cell boundaries, containing many- 
nuclei of varying shapes embedded in a deeply staining 
vacuolated granular cytoplasm, the whole resembling collec- 
tions of fused giant cells. This outer layer of cells is called 
the syncytium, and from it small protoplasmic processes, 
the syncytial buds, project. The surface of the syncytium 
in properly fixed specimens is covered with delicate rod-like 
projections resembling cilia, the stereocilia. These are pres- 
ent even in the syncytial cells of tumors of the chorionic 
type occurring in the teratomata in males. 

In the later periods of normal pregnancy, the cell layers 
covering the chorionic villi are, as a rule, less distinct than 
at some earlier period, the Langhans' type tending to dis- 
appear after the third month. The cells covering the villi, 
possibly by virtue of a proteolytic ferment, penetrate the 
maternal decidua lining the uterus, mingling with its cells, 
and deeply invade the structure of the uterine wall. Lang- 
hans', but more especially syncytial, cells may be found 
deep among the muscles of a normal pregnant uterus. Such 
syncytial wandering cells also invade the walls of the blood- 
vessels, thus causing hemorrhage and thrombosis, and may 
enter the maternal circulation and be carried as emboli to 
various viscera, especially the liver and the lung.^ 

It may seem a strange phenomenon that one group of 
cells of the body are capable of dissolving another group, or 
penetrating tissues to a very considerable distance, but a 
moment's thought will show that these cells differ from any 
other type in the human body, inasmuch as they are not 
purely autogenous, but are partly composed of elements 
from an entirely strange source, notably the spermatozoa 
of the male, so that they are not perfectly adapted to the 

iSchmorl: Verhandl. d. deutsch. path. Gesellsch., 1904, viii, 39; Schot- 
ten: and Veit: Ztschr. f. Geburtsh. u. Gynak., 1903, xlix, 2*10. 

183 



female in whose body they develop. It is thought that 
many of the phenomena which are connected with the dis- 
appearance of the chorionic villi at the end of pregnancy 
may be explained by the fact that these cells as they pass 
about the body incite substances which ultimately work 
their destruction when the need for them has ceased to 
exist. The fact that fully developed and morphologically 
highly malignant tumors derived from the chorionic villi 
may also undergo spontaneous regression in a very much 
larger percentage than is observed in similar tumors derived 
from the epithelium or connective tissue of the body has 
also led to the view that possibly these tumors themselves 
may incite a reaction against their own tissues which may 
ultimately destroy the delicate balance between progressive 
growth and the regression caused by lack of sufficiently large 
quantities of nourishment such as are required for all 
tumors. Whatever the explanation, it is certain that a con- 
siderable number of cases of chorionepitheliomata have 
been observed to disappear spontaneously.^ 

The tumors derived from chorionic epithelium appear, 
in the vast majority of cases, in the uterus following normal 
pregnancy, a miscarriage, or the passage of an hydatid 
mole. Such choriomata may occur, also, long after pregnancy 
has terminated, in fact, after the menopause has occurred, 
and unquestionably are derived from fragments of chorionic 
epithelium which have remained in a quiescent state in the 
uterus. Chorionepithelioma may arise, also in an ectopic 
pregnancy in the Fallopian tube or ovary. Another very 
rare type of chorionepithelioma may appear in the female 
in teratomatous tumors of the ovary, as well as in the male 
in the complex growths of the testis, and chorionepithe- 
lioma has also been seen in the thoracic teratomata in a 

ipieischmann: Monatschr. f. Geburtsh. u. Gynak., 1905, xxi, 353; 
Schotten and Veit: Ztschr. f. Geburtsh. u. Gynak., 1903, xlix, 210; 
Teacher: Jour. Path, and BacterioL, 1908, xii, 487. 

184 



few instances. In general, chorioma of any type is an in- 
frequent form of tumor; probably not more than 800 in- 
stances have been recorded to date. 

Whether the chorionepitheliomata are directly derived 
from the normal chorionic villi, or whether some prelimi- 
nary change has to occur in these cells before a tumor can 
arise is not yet fully settled. A few tumors have been 
described which were apparently due to emboli of chorionic 
villi occurring during a normal pregnancy, but the difficul- 
ties of interpretation are so great that these observations 
cannot be regarded as finally settling the question. The 
usual assumption is that some preliminary alteration takes 
place in the placenta before the chorionepithelioma arises. 
The most important pathological change of this type is the 
hydatid or hydatidiform mole. (The name means only a 
mass of tissue resembling the hydatid or tape-worm cyst. 
It is an old descriptive term and has been current for many 
years.) The process consists merely in a swelling and 
edema of the chorionic villi and a proliferation of the sur- 
face epithelium. This may be confined to the Langhans* 
cells; or large masses of syncytium may be formed. The 
cause of this transformation is not known. The mole may 
be cast off with a fetus, or there may be no trace of an 
embryo. The mole may remain after the birth of the fetus, 
or be passed shortly after the fetus is delivered ; or, in other 
conditions, it may remain for a long time in the uterus. At 
the same time, there is apt to be present in the ovaries 
large lutein cysts. Metastases of the fragments of the 
mole tissue may take place throughout the body, in some in- 
stances giving rise to a tumor with the characteristics of 
the original structure.^ Nearly 50 per cent, of chorion- 
epithelioma have been observed to follow moles.^ This change 

iFrank: R. T., Am. Jour, Obst., 1911, Ixiv, 435. For a detailed study 
of hydatids, see Essen-MoUer: Studien uber Blasenmolen, Wiesbaden, 
1912. 

^Pollason and Violet: Ann. de g-ynSc. et d'obst., 1913, Ixx, 257. 

185 



occurs usually four to five months after the last menstrua- 
tion. The tumors are more frequent in those who have had 
repeated pregnancies. In rare instances chorioma may ap- 
pear a number of years after the last pregnancy^ or even 
after the menopause. 

The usual classification of the choriomata has been 
into ''typical'' and "atypical," the typical being those forms 
composed of structures fairly closely resembling the normal 
villi, while in the atypical are grouped the neoplasms in 
which the Langhans' or the syncytial cells form the pre- 
dominant portion of the tumor and are arranged entirely 
without any regularity. Ewing^ has proposed a further 
division into chorioadenoma, choriocarcinoma, and syncytial 
endometritis ; but this has not received wide adoption. 

Microscopically, the tumors vary according to the con- 
ditions in the uterus. If the m.ole still remains, or portions 
of it, the clear grape-like masses give a clue to the nature 
of the tumor. If the mole has been passed, the wall of the 
uterus may be covered with a rough reddish or purplish 
shaggy mass involving the uterine wall m-ore or less com- 
pletely. The latter is, in almost all instances, very much 
thickened. The tumor may even competely perforate the 
uterus.^ If there is any remaining endometrium, it may be 
normal, though usually it is entirely eroded and destroyed 
by the tumor. In the atypical or choriocarcinomatous type 
the uterus is only moderately enlarged and may be even 
normal in size if the tumor is small. No remnants of mole 
tissue can be discovered in the gross. The tumor forms a 
firm dense mass containing hemorrhagic areas and covered 
with clots. It may adhere to one portion of the uterus or 
diffusely involve the whole endometrium, and is much firmer 

iQuterbridge: Am. Jour. Obst., 1915, Ixxii, 952; Moschcowitz, E.: 
Proc. New York Path. Soc, 1910, x, 186. 

^Ewing-: Surg-., Gynec, and Obst., 1911, xi, 366. 

^Curtis and Qui: Ann. de gynec. et d'obst., 1913, Ixx, 321. 

186 



{ 



\ 



and more compact than the previously described type. It 
is usual to find very extensive invasion of the uterine blood- 
vessels, and not at all uncommon to see large masses grow- 
ing out through the veins of the pelvis. In this particular 
type metastases are frequent all over the body. Even the 
brain is involved in ten per cent, of the cases. Vaginal im- 
plantations are noted in a fifth of the cases, and pulmonary 
tumors in one-third. In a smaller group of tumors, the 
atypical chorioma of Marchand, the uterus does not show a 
discrete tumor, but the wall is infiltrated by large syncytial 
wandering cells. To this process the term syncytioma has 
been applied. This type does not form metastases and has 
been cured by deep curettage. 

Microscopically, in the "typical" tumors or chorioade- 
noma, the remnants of the hydatid mole are usually present, 
and the growth is made up of mixtures of different propor- 
tions of syncytium and Langhans' cells forming compact 
masses. The formation of syncytium seems to be stimu- 
lated by the presence of blood so that the greatest develop- 
ment of the syncytial masses is around the hemorrhagic 
part of these tumors. The syncytial buds may be very 
abundant and form a considerable proportion of the neo- 
plasm. In properly preserved specimens stereocilia can be 
found on the periphery, and even lining the cavities in the 
syncytial cells. All transitions exist between the normal 
villi, hydatid mole, and tumor, and there are intermediate 
phases in which it may be exceedingly difficult to determine 
whether the tumor is malignant' or not, and only careful 
study of the uterine wall, either from very deep curetting, 
which is not without its danger in the softened condition 
of the viscus, or the opportunity to examine the whole speci- 
men after hysterectomy, will enable a definite conclusion to 
be drawn. Unfortunately, owing to the malignancy of the 
growth, such determination is only an academic question. 
In the more malignant type, the choriocarcinoma, the tumor 

187 



consists of glandular masses of syncytium mingled with is- 
lands of actively growing Langhans' cells. The only connec- 
tive tissue is that of the organ in which the tumor is 
formed. Mitoses are present only in the Langhans' cells. 
Microscopic evidence of the invasion of the uterine sinuses 
and other tissues is abundant. There is little difference be- 
tween the metastases in the lungs and other organs and the 
primary growth. The pulmonary and other metastases may 
consist of little but blood and fibrin with scattered masses 
of syncytial cells and a few cells of the Langhans' type. 

The clinical course of the disease differs in the different 
types. The forms which follow the hydatid moles, chorio- 
adenoma, are fairly benign ; for example, eleven out of four- 
teen in one series recovered after hysterectomy; but local 
metastases occur and should be excised if possible, or if 
not, treated by radiation, it being remembered that a con- 
siderable proportion of tumors of this type have been known 
to disappear spontaneously. The more malignant type is 
wholly different. There is no record of operative cure. The 
metastases take place so early that by the time the diag- 
nosis is made operative measures are out of the question. 
The purely syncytial form, involving the endometrium only, 
is less malignant and a number of patients have recovered 
after simple curettage.^ 

In most instances, the diagnosis is perfectly simple. 
The hydatid mole can be diagnosed by mere inspection of 
the gross material. A compact mass of syncytial and Lang- 
hans' cells curetted from a bleeding uterus four or five 
months after pregnancy is extremely suspicious of chor- 
ionepithelioma, but enough material for diagnosis must be 
removed from the uterus, since these tumors are always 
hemorrhagic and it is possible that nothing but blood clot 
will be sent for examination, even if a tumor is present in 

^Hitschmann und Christofoletti: Wien. klin, Wchnschr., 1911, xxiv, 
655 and 705; v. Velits: Ztschr. f. Geburtsh. u. Gynak., 1904, Hi, 301. 

188 



the uterine wall. If hemoptysis has been noted, pulmonary 
metastases are present. Confusion with placental tissues 
should not arise ; the latter are much more apt to be necrotic 
and infected, and to show extreme degenerative changes; 
while the tumor cells will be well preserved ; and the Lang- 
hans' cells are apt to show mitotic figures. In doubtful 
cases, where a differential diagnosis has to be made between 
a benign mole and a chorioadenoma, large numbers of sec- 
tions should be examined, in order to find, if possible, evi- 
dence of invasion of the uterine sinuses or penetration of 
the musculature. Discretion must be used, however, and 
if possible, a second curettage should be done in two to 
three weeks, because in many instances a slight amount of 
penetration may occur even under normal conditions, but if 
it is present in a second specimen it may be taken to indi- 
cate malignancy. If there is any question, however, it is 
better to make a diagnosis of malignancy and treat the 
case accordingly rather than to temporize and see the pa- 
tient die of metastases. 

HYPERNEPHROMA 

A peculiar and morphologically characteristic type of 
tumor frequently arises in the substance of the kidney, in 
the adrenal, or from adrenal fragments displaced in other 
organs, such as the liver and testicle. These tumors are 
wholly different from any other form of neoplasm, and, 
hence, have been given a special group name. The basis 
for our knowledge regarding them was laid by Grawitz in 
1883,^ and the name ^'hypernephroma" is due to Birch- 
Hirschfeld. The tumors occur most frequently in the kid- 

Klrawitz: Die sogenannten Lipome der Niere, Virchows Arch. f. path. 
Anat., 1883, xciii, 39. 

189 



ney, where they are, in their earliest stages at least, en- 
capsulated, and only later involve the substance of the 
organ. They evince an especial aptitude to involve the 
renal veins and extend throughout the body, often metas- 
tasizing in the bone marrow, giving rise to spontaneous 
fractures, and to vascular pulsating growths whose physi- 
cal peculiarities led to their designation as bone aneurysms. 
On section the tumors are exceedingly characteristic, being 
of a dull yellowish color often mottled with numerous 
hemorrhagic areas. Many of them are small and relatively 
benign, others are highly malignant. In a number the 
central portion of the growth is fibrous and surrounded by 
a more or less well marked cortical portion, as was first 
insisted upon by Grawitz. The peritoneal tissues and lymph- 
nodes are early involved in the malignant forms. 

Microscopically, the younger tumors resemble very 
much the adrenal gland. The cells are arranged in small 
groups, separated by fine strands of connective tissue. The 
cytoplasm is granular and contains numerous lipoid and 
glycogen granules, which give the cells of the fixed prepa- 
ration a foamy structure. In many instances, the cells are 
arranged about the abundant capillary network, which ex- 
plains their opportunity for early invasion of the vessels. 
While usually the cells of tumors are about the same size, 
multinucleated giant cells of granular structure may be 
abundant, or the tumor may be composed almost wholly of 
such cells, which also make their appearance in the meta- 
stases. In some cases, the structure imitates with great 
closeness the structure of carcinoma ; in others, the spindle- 
cell type suggests sarcoma. Chromaffin cells which take a 
brown stain with chrome salts may be present. Some ex- 
amples of the tumors are composed of papillary structures, 
and the cells of these are often clear and show practically 
no cytoplasmic remains. Many pathologists consider that 
these tumors, or at least many of them, should be classified 

190 



as carcinomata or adenocarcinomata of the kidney,^ yet even 
those who hold most firmly to the carcinoma point of view 
acknowledge that morphological differentiation of many of 
these growths is difficult or impossible, so that for the pur- 
poses of classification all may well be considered under the 
old name of hypernephroma until our knowledge concern- 
ing this peculiar group is much greater than at present. 

The diagnosis of a certain number of these tumors can 
be made by gross inspection, especially if the growth is 
small and does not show much hemorrhage, for the yellow, 
opaque appearance of the cut surface is characteristic. 

Microscopically, the clear cells, the presence of doubly 
refracting lipoids when fresh frozen sections are examined 
under a polarizing microscope, the large amount of glycogen, 
which is best seen with specimens fixed in alcohol and 
treated with iodine, or stained with Best's carmine, the 
cl6se relationship of the cells to the capillaries, and the 
general topography of the tumor are quite characteristic, 
and should lead to no confusion with other tumors. In fact, 
the diagnosis of hypernephroma has frequently been made 
from metastases in the skin or in the organs when no 
tumor of kidney origin had been suspected. 

TERATOMA 
(Tumors Arising from Congenitally Displaced Tissues) 

While in the early days of pathology the study of the 
teratomata (a word which is derived from the Greek teras, 
meaning a marvel or a monster) was confined largely to 
grossly malformed embryos, at the present time it is being 

^Ewing: Neoplastic Diseases, Philadelphia, 1919; Stoerk, O.: Zieglers 
Beitr., 1908, xliii, 393; Sisson, W. R.: Zieglers Beitr., 1910, xlix, 476; Wilson 
and Willis: Jour. Med. Research, 1911, N. S. xix, 73; Ipsen, J.: Zieglers 
Beitr., 1912, liv, 233; Fraser, A.: Surg., Gynec, and Obst., 1916, xxii, 645; 
Glynn, E. E.: Quart. Jour. Med., 1912, v, 157; Dunn, J. S.: Jour. Path, and 
BacterioL, 1913, xvii, 515; Jacobson, V. C. and Goodpasture, E. W.: Arch. 
Int. Med., 1918, xxii, 86 (bibl.); Scudder: Ann. Surg., 1906, xliv, 851. 

191 



more and more realized that tissues, also, may be mal- 
formed, and that the puzzling complex tumors of the body- 
are best explained by congenital displacements, either of 
single tissue, of small masses of closely related tissue, or 
even of a great variety of structures, and that others still 
are possibly derived from the development of the sex cells, 
either male or female, in their respective organs. As a 
rule, the structures derived from the displacement of 
a single tissue, such as the epidermoid cysts, congenital 
moles, and angiomata, are not considered among the tera- 
tomata, nor are the complex tumors occurring in or about 
the salivary glands and in the kidney grouped with them; 
but in one sense all of these tumors belong together. While 
there is but little question as to the underlying nature of 
the conditions attached to the formation of united twins 
or even of the complex parasite composed of a partially 
developed twin adherent to a normal individual, there has 
been much doubt cast on the possibility of the persistence 
of embryologically displaced fragments, the hypothesis 
upon which Cohnheim based his theory of tumor develop- 
ment. Nevertheless, in recent years, investigations of a 
histological type have thrown much light on the presence 
of cell complexes derived from early embryonic existence. 
Some of the most striking examples of the persistence of 
fragments of tissue or organs are offered by the minute 
study of the urogenital system of the female, ° where the 
very complexity of organ development and migration makes 
it possible for cells or groups of cells to be left behind in 
the course of the wandering of the organs to their final 
position. A large number of definite observations confirm- 
ing the persistency of remnants of the Wolffian or Gaert- 
ner's ducts, now exists. The presence of glandular remains 
of these ducts and fragments of adrenal tissue have been 
frequently noted about the ovary and in the broad and 
round ligaments. Analogous displacements of portions of 

192 



the pancreas, fragments of which are not uncommon in 
the stomach or intestinal wall, at the umbilicus, or in 
Meckel's diverticulum are now on record. Fragments of 
thyroid tissue are not infrequently found at the base of the 
tongue, or along the thyroglossal duct. Epithelium, both 
of squamous and cylindrical varieties, is not infrequent in 
the neck, and may be recognized as derived from remnants 
of the branchial clefts. If such well marked tissues are 
fairly frequently displaced, it is obvious that a like exten- 
sion of this process may explain, for example, the salivary 
tumors in which striated muscle, cartilage, bone, and 
squamous epithelium are present, besides a large number 
of other structures both epidermal and mesodermal. The 
time at which this displacement occurs will determine, to 
a certain extent, the type of development which they under- 
go as they become neoplastic in nature. So, too, the com- 
plex tumors of the kidney which contain cartilage, striated 
muscle, and other portions of tissues which do not nor- 
mally occur in the organ, together with glandular remnants, 
should be interpreted in this way, rather than by recourse 
to an inclusive broad theory of metaplasia, which by break- 
ing down all histological boundaries explains nothing, but 
merely avoids the problem. The displacement theory has 
been offered for some of the complex tumors developing 
elsewhere. The teratomata of elaborate structure, such as 
occur in the ovaries, testicle, sacrum, or mediastinum, do 
not belong in the class due to tissue displacements alone, 
but are presumably derived from cells left in these regions 
at a date so early in embryonic development that they re- 
tain a histological totipotency. In pursuance of this per- 
haps somewhat irregular classification of tumors of dis- 
placed tissue, we will take up first those in which single 
structures are removed from their normal position, the 

193 



epidermoid cysts of the skin. Congenital moles and angio- 
mata have been described in another place. The complex 
salivary tumors will then be considered, next cystic or 
teratoid remnants derived from certain of the fetal tissues 
in the fissures in the body, and, finally, the complex tumors 
arising from totipotent cells. 

DISPLACEMENTS OF SINGLE TISSUES 
Epidermoid Cysts 

Epidermoid cysts are occasionally found in the palmar 
surface of the hand and the fingers. They are small, hard 
cysts, rarely measuring over a centimeter in diameter, and 
are due to the traumatic implantation of epithelium under 
the surface of the skin.^ The cells so transplanted grow 
and form a smooth-walled cyst lined with one or two layers 
of squamous epithelium; or, in the case of the small cysts, 
an epithelial pearl may develop from the center, forming 
a hard mass. Cases have been seen where a small steel or 
wood splinter made up the center of the cyst, an epithelial 
layer having been formed about it;^ and such cysts have 
also followed gun-shot wounds of the hand. It is believed 
that occasionally these cysts may arise by epithelial meta- 
plasia in traumatically irritated sweat or sebaceous glands 
or hair follicles. The contents of the cysts are usually 
composed of fatty matter and flattened epithelial cells. 

They are distinguished from the true dermoid cysts 
by the fact that the latter, which are formed during em- 
bryonic life, almost always show in a more or less perfect 
manner the structure of the skin with papillary bodies, oc- 
casionally hair, and sweat and sebaceous glands. 

iPels-Leusden: Deutsch. med. Woch., 1905, xxxi, 1340 and 1578; Hesse: 
Traumatic epithelial cysts, Beitr. z. klin. Chir., 1913, Ixxx, 494. 
2Wiemann: Centralbl. f. Chir., 1902, xxix, 578. 

194 



\ 



Dermoid Cysts 



The name dermoid cyst is applied to those epithelial 
cysts whose lining wall contains all the structures of the 
skin. The presence of sweat and sebaceous glands and hair 
follicles, as just stated, separates the dermoid cysts from 
the epidermoid variety. 

Dermoid cysts occur in various parts of the body, 
usually in relation to the skin. They are especially frequent 
on the face, and are perhaps most often met with at the 
outer angle of the eye and just above the orbit, where they 
are derived from epidermal inclusions left during the 
closure of the orbital fissure present in this region in early 
fetal life. They also, but more rarely, occur in the parotid 
region from remnants of epidermis left during the closure 
of the first branchial cleft. They are found, also, on the 
bridge of the nose and roof and floor of the mouth, in the 
orbit, in the deeper tissues of the lateral aspects of the 
neck, in the breast, in the mediastinum, at the navel, in the 
cellular tissue of the pelvis, in the abdominal cavity, 
and on the sacrum. Occasionally they are found inside the 
skull, either extra- or intradural in situation and may be 
still connected with the scalp by a strand of connective 
tissue reaching to the nearest suture or to another external 
cyst. 

Small dermoid cysts are occasionally found in the an- 
terior mediastinum, and larger growths may occupy a con- 
siderable portion of the pleural cavity. Such cysts are in all 
probability derived from the congenital displacement of 
epidermal remnants before the closure of the anterior 
thoracic wall. 

195 



In addition to cysts left by invagination of the anterior 
thoracic wall, a certain group are derived in all prob- 
ability from the thymus, which is an epithelial organ. 
Ciliated cysts of the mediastinum are due, in all probability, 
to diverticula of the trachea. Ciliated cysts, sometimes 
multilocular, also, have been found in the posterior portion 
of the thorax, and are due to fetal remnants of the lung 
or of the esophagus, which in fetal life is lined with ciliated 
epithelium. 

The simple epidermoid tumors of the dorsal aspect of 
the sacral region are rare, and are probably due to rem- 
nants of epithelium left during the closure of the neural 
canal. Small dermoid cysts or fistulae lined with epidermis, 
however, are quite often seen in a position corresponding 
to the foveola coccygea.^ These last anomalies are generally 
considered to be due to an imperfect obliteration of the 
post-anal gut, which at an early stage of embryonic de- 
velopment is connected with the common cloacal opening. 
In normal persons the position of this embryonal vestige 
is shown by the presence of a small dimple over the coccyx, 
from which runs a fibrous band connecting with the coccyx. 

The structure of the epidermoid cysts in this region is 
similar to that of those seen in other places. They often 
contain hair and fairly well marked epidermal lining. They 
not infrequently suppurate, owing to infection, and dis- 
charge their contents, and even the epithelium may be en- 
tirely lost if the process be continued for a considerable 
time; so that the diagnosis must rest very largely upon 
the macroscopic presence of hair in the contents of the 
cyst or as discharged from the sinus after the cyst ruptures 

^Markoe and Schley: Am. Jour. Med. Sc, 1902, cxxiii, 820. 

196 



or is opened. The sinuses in the same situation show a 
similar structure and are lined with epidermis carrying fine 
hairs, and are frequently the site of inflammatory pro- 
cesses. It is often difficult to demonstrate any epithelial 
remnants lining the sinuses as the cells are usually de- 
stroyed by the inflammatory process. Occasionally, how- 
ever, the hairs remain fixed in the granulation tissue, often 
surrounded by giant cells, and give a clue to the correct 
anatomical relationships of the tissues. If they cannot be 
found one must fall back upon the clinical history and 
anatomical position of the sinus for a probable diagnosis. 

Macroscopically, the majority of the dermoids do not 
measure over 1 to 2 cm. in diameter but occasionally, 
especially when present in the internal parts of the body, 
they may reach 10 cm. or more. On cutting into them, a 
fatty paste escapes, which is composed largely of desqua- 
mated epithelium, sebaceous matter, and cholesterin derived 
from the gradual breaking down of the lining membrane 
of the cyst, plus secretion from any of the glands present 
in the wall. The lining is usually smooth, occasionally a 
considerable growth of hair may occur. The skin over the 
mass is freely movable, and if they lie near bone there may 
be a depressed cavity at the site of the tumor. 

Microscopically, the wall is composed of squamous epi- 
thelium showing either sweat or sebaceous glands or hair 
follicles, or all of these combined. Occasionally, cysts are 
found which have become infected or inflamed, and in this 
case the epidermal lining of the wall may be replaced by 
granulation tissue. Sometimes the tissue so formed is 
filled with giant cells^ surrounding either cast-off epithelium 
or hair. The contents may undergo calcification. 

iBohm, H.: Virchows Arch., 1896, cxliv, 144 and 276. 

197 



TUMORS ARISING IN EMBRYONIC DISPLACEMENTS 
OF SEVERAL TISSUES 

Complex Tumors of the Salivary Glands^ 

There is a peculiar group of tumors which occur in 
the salivary and lacrimal glands, in the palatal region,^ in 
the lips, and occasionally elsewhere, all of which have simi- 
lar structure and are not closely related in morphology with 
any of the well known types of tumors. They are consid- 
ered under the fibro-epithelial group, though, as they prob- 
ably arise chiefly from malformations and displacements 
during embryonic life, they are by many authors classed 
with the teratoid tumors. Originally, under the influence 
of Billroth and of Volkmann,^ these were called cylindro- 
mata or endotheliomata. The tumors may occur in the 
center of the gland, being entirely surrounded by normal 
gland, or they may be separated by a considerable distance 
from any salivary structures. Embryological studies have 
shown* that in the development of the parotid gland there 
are many small areas of gland structure which appear in 
the embryo and yet never progress further as the gland 
develops. This accounts, for example, for tumors seen on 
the inner surface of the cheek at the opening of Stenson's 
duct. 

Most of the tumors are encapsulated, firm, elastic, nod- 
ular, lobulated masses. They are apt, however, especially 

^The most important monograph on these tumors is that by Heineke: 
Deutsch. Chir., Stuttgart, 1913, xxxiii (very complete bibl.) See, also, 
Wihns: Die Mischgeschwulste, Leipzig, 1897; Wood: Ann. Surg., 1904, xxxix, 
57 (bibl.); Wilson and Willis; Am. Jour. Med. Sc, 1912, cxliii, 656 (bibl.) 

^Sturgis, M. G.: Mixed-cell tumors of soft palate, Surg., Gynec, and 
Obst., 1914, xviii, 456. 

8Volkmann: Deutsch. Ztschr. f. Chir., 1895, xli, 1. 

*Schulte: The Development of human salivary glands, Studies in Cancer 
and Allied Subjects, New York, 1913, iv, 25. 

198 



in the parotid group, to involve the facial nerve and pene- 
trate the gland substance by blunt prolongations. They 
are most frequent in the parotid, rarer in the sub-maxillary, 
and very infrequent elsewhere. The color and structure of 
the cut surface are extraordinarily variable. The surface 
may be of a pearly bluish color, in which case the tumor 
will be found to be composed largely of cartilage ; here and 
there may be more or less opaque yellowish areas which 
represent collections of epithelial cells. On the other hand, 
the tumor may be very soft and composed largely of mucoid 
tissue, which may ultimately liquefy with the formation 
of small cysts containing fluid. Some of the tumors are 
hard, fibrous, and even calcified or bony. These neoplasms 
are very slow growing and, as a rule, when properly ex- 
tirpated do not recur. The statistics of a large number of 
cases treated show that postoperative recurrence does not 
take place in more than one-fourth of the tumors removed. 
Metastases are rare and occur usually in the regional 
lymph-nodes. The metastatic tumor is composed of a single 
type of cell, the epithelial form which gives the character 
to the tumor; these cells are small with small nuclei and 
deeply staining cell body. Excision of involved lymph- 
nodes may result in a permanent cure. It has been shown, 
also, that some of these tumors are quite susceptible to 
the action of radium,^ in contradistinction to the carcino- 
mata and sarcomata. 

Microscopically, the structures vary as much as does 
the gross appearance of the tumor. The most striking type 
is composed of tubules of epithelial cells, provided with a 
lumen filled sometimes with a thick coagulated pink stain- 
ing material, sometimes with mucoid substance staining 
blue with hematoxylin. Well marked epithelial pearls com- 
posed of prickle cells have been found in a considerable 

^Weil, R.: Jour. Am. Med. Assn., 1915, Ixv, 2138. 

199 



proportion of the tumors. The amount of stroma varies 
extraordinarily; it may be extremely abundant or very 
scarce. The structure, also, is correspondingly varied. Mu- 
coid tissue is common and contains only a few stellate 
cells. The connective tissue frequently undergoes hyaline 
degeneration. Cartilage of the hyaline type is frequent 
and fuses with the other tissues, and does not as a rule 
form discrete masses. 

While these tumors may grow slowly and even remain 
innocuous for twenty or thirty years, they occasionally 
undergo changes which are evidenced by a sudden increase 
in growth rate and rapid involvement of the surrounding 
tissue, with metastasis to regional nodes. Under these cir- 
cumstances squamous-cell epithelioma and spindle-cell sar- 
coma have been found superimposed on a mixed tumor. 
Such alteration in type is fortunately rare. 

Diagnosis is easy. The intermingling of cartilage, mu- 
coid, and richly cellular fibrous tissue, with the peculiar 
glandular or branching trabeculae of the parenchyma are 
seen in no other tumor. 

f Complex Tumors of the Kidney 

There occurs in the kidney a group of tumors whose 
complex nature points to a simultaneous segregation of 
muscle, bone, and other tissue and nephrogenous material.^ 
These neoplasms usually occur in infants, but in a few in- 
stances have been seen in the first decade of life, and in 
one case a tumor was reported in a patient of fifty-four. 
The tumors lie within the kidney, surrounded by its cap- 

iHedren, G.: Zieg-lers Beitr., 1907, xl, 1 (bibl.); Weingraf: Virchows 
Arch. f. path. Anat., 1913, ccxiv, 161 (bibl.); Busse: Virchows Arch. f. path. 
Anat., 1899, clvii, 346, 377; Muus: Virchows Arch. f. path. Anat., 1899, civ, 
401; Wilms: Die Mischgeschwulste, Leipzig, 1899-1902; Buerger and Laut- 
man: Am. Jour. Surg., 1914, xxviii, 453. 

200 



sule, and are usually sharply separated from the remnants 
of kidney structure. In exceptional cases, the growth is 
entirely separate from the normal kidney substance. Many 
of the tumors reach an extraordinary size when the kidney 
is compared to the body of the infant in which it is present. 
The tumor is soft, often lobular, and divided by bands of 
connective tissue into areas of different consistency, and 
cysts are not at all uncommon. Hemorrhages and necrosis 
are rather late. Metastases into the liver and lungs are 
often seen, but these tumors do not involve the blood- 
vessels as frequently as do the hypernephromata. 

Microscopically, the distinctive features of the tumor 
are the great variety of embryonal structures which are 
present. The mass of the tumor is usually made up of a 
richly cellular embryonal connective tissue which may con- 
tain striated muscle, areas of spindle cells resembling sar- 
coma, myxomatous tissue, fat, cartilage, and occasionally 
bone. Scattered throughout the tumor are often areas of 
gland-hke tubules which resemble the renal tubules, and 
sometimes imperfectly formed glomeruli. The cysts which 
may be present are lined by cubical or squamous epithe- 
lium. The metastatic deposits are usually of small round 
or spindle cells, resembling sarcoma, but in one instance, 
striated muscle cells were found in a metastatic lung neo- 
plasm. 

The obvious explanation of the origin of these com- 
plex tumors is the simultaneous displacement of nephro- 
genous tissue with cells from the myotomes, and rudiments 
of skeletal structures which account for cartilage and bone. 
These, if mixed with the early embryonic substance of the 
kidney, explain most of the histological peculiarities of the 
tumors. A small group of pathologists are inclined to in- 
voke metaplasia to account for the whole process, an ex- 
planation which explains nothing. 

201 



Complex Tumors of the Uterus and Vagina 

A group of complex tumors are found in the uterus and 
vagina which closely resemble those seen in the kidney. 
They occur usually as soft, often polypoid tumors which 
protrude from the cervix or arise from the wall of the 
vagina. They are, in general, simpler histologically than the 
kidney tumors, and consist chiefly of a soft myxomatous 
or sarcomatous stroma containing cartilage and often 
striated muscle. In a few instances, glandular remnants 
have been found, and, in one case, carcinoma. 

Microscopically, the tumors present nothing of especial 
interest, except that the muscle fibers are those of the 
embryonic type and show all of the curious modifications, 
such as club-shapes and branching forms, which are char- 
acteristic of this kind of muscle. The tumors are highly 
malignant, and the type of neoplasm is that of a sarcoma^ 
with the exception noted above. 

Similar complex tumors containing cartilage, striated 
muscle, fatty tissue, and occasionally remnants of the nerv- 
ous tissues, are found in the bladder. Dermoid-like tumors, 
also, usually of a complex type, occur in this viscus. These 
are rare tumors, and sometimes are malignant, (osteo- 
chondro-sarcoma) ; others simply affect the patient because 
of their volume in the bladder or by the cystitis caused by 
the presence of hair. 

In the liver, also, similar tumors usually containing 
cartilage, and adenomatous structures, have been found in 
v^ery rare instances.^ 

^McFarland: Sarcoma of the vagina, Am. Jour. Med. Sc, 1911, cxli, 570 
(bibl.); Jessup: Proc. New York Path. Soc, 1913, xiii, 81. 
^Hippel: Virchows Arch., 1910, cci, 32"6. 

202 



TUMORS ARISING IN EMBRYONIC REMAINS OF 

ORGANS 

Branchiogenetic and Other Congenital Cysts 

The complex processes which take place in the forma- 
tion of the various structures of the neck and face result 
in an extensive group of malformations of greatly varying 
types.^ Fissures, cysts, dermoids, fistulae, and tumors, all 
seem to be correlated with the complex anatomical condi- 
tions underlying the final construction of this region. The 
abnormalities connected with the first branchial cleft are 
found chiefly in the aural and submaxillary regions; they 
consist largely of malformations of the ears, aural fistulae, 
aberrant cartilaginous remnants of various types; a few 
dermoid cysts have been reported in the neck and in the 
floor of the mouth, and do not differ from those found else- 
where. Their walls do not contain lymphoid tissue as do 
the walls of those of the second cleft, from which the great 
majority of branchial fistulae and cysts originate. Typo- 
graphically, these lie anterior to the stemomastoid muscle 
and may occur at any point from the external ear forward 
to the hyoid bone. The cysts and fistulae vary a good deal, 
when lined with epidermis their contents are usually seba- 
ceous, and they may contain hair. Some are lined with cylin- 
drical epithelium and usually have mucoid contents ; others 
have both varieties of epithelium ; while still another group 
has ciliated cells lining the wall. The tissue surrounding 
the sac of these cysts usually contains abundant lymphoid 
tissue, except in the dermoid group. Thyroid alveoli are 
seen occasionally, and striated muscle and islands of carti- 
lage are not infrequent. Fistulae may form by the rupture 

^For a general study of the congenital fistulae and cysts of the neck, 
see V. Kostanecki and v. Mieleckl: Virchows Arch. f. path. Anat., 1890, cxx, 
385; 1890, cxxi, 55, 247; and Aschoff: Lubarsch-Ostertag, Ergebn. d. allg. 
Path., 1895, li, 456. 

203 



of the cyst on the surface or may extend from the skin 
to the pharyngeal cavity. The chief clinical interest of 
these cysts, aside from the discomfort which they produce, 
is the possibility of the origin of carcinoma in them. 

Another group of cysts is related to the thyroglossal 
duct which runs from the foramen caecum at the base of the 
tongue to the middle lobe of the thyroid. This duct is 
lined with squamous or ciliated epithelium. The upper 
portion of the duct may remain patent or cysts of various 
types may form along its course. Islands of thyroid tissue 
accompany it and frequently give rise to considerable 
tumors in the substance of the tongue; rarely parathyroid 
tissue, also, may be found.^ 

The cystic hygromata of the neck, also, are probably 
connected with the developmental complexities of this 
region.2 

The lower clefts rarely give rise to cysts, though possi- 
bly some of the dermoids of the upper portion of the tho- 
racic cavity may be related to these fetal remnants. 

The congenital cystic kidneys, though not usually in- 
cluded under embryonal malformations, really belong here, 
for according to Ribbert they are due to lack of junction be- 
tween the tubular and the glomerular portions of the renal 
tubules with secondary formation of cysts. 

TUMORS ARISING IN MISPLACED BLASTOMERES 

Complex Tumors of the Testis.^ 

The complex tumors of the testis form a peculiar group 
pathologically ; and the present tendency is to consider that 
most of them are derivatives of totipotent blastomeres or 

iWood, F. C: Proc. K'ew York Path. Soc, 1916, xvi, 84. 
2Smith, O. C: Jour. Am. Med. Assn., 1914, Ixii, 522. 
sDebernardi: Zieglers Beitr., 1907, xl, 534 (bibl.) ; Frank, A.: Frank- 
furt. Ztschr. f. Path., 1912, ix, 206 (bibl.). 

204 



sex cells/ and also that such tumors as are composed of a 
single type of tissue are merely those in which a one-sided 
development of a tridermal tumor has taken place.^ What- 
ever may be the ultimate fate of this hypothesis the fact 
remains that in almost all of the tumors of the testicle 
remnants of cartilage, squamous epithelium, and other 
structures suggestive of teratoid origin are present. The 
undescended testicle is even more liable to exhibit tumors 
of teratoid nature than is the organ in its normal position.^ 

Three main groups can be distinguished in the teratoid 
testicular growths. First, highly complex teratomata with 
adult tissue; second, tumors of mixed tissue without any 
evidence of organ formation but frequently containing chor- 
ionepitheliomatous changes; third, a group in which the 
structure is a type of neoplastic tissue resembhng car- 
cinoma though teratoid remnants are often present. The 
last used to be considered as sarcomata and have also been 
called seminomata by Chevassu.* Testicular teratomata of 
the first group are relatively infrequent. They usually con- 
tain abundant cysts and fragments of embryonic organs; 
but teeth are rarely seen. 

Microscopically, these tumors resemble very closely the 
ovarian dermoids. All the types of structures that are pres- 
ent in the dermoids are found, for example, brain, choroid 
plexus, ganglion cells, neuroepithelial structures, glia, glan- 
dular tissues of various sorts, striated muscle, fragments 
of the gastrointestinal tract surrounded by involuntary 
muscle, canals containing cartilage and lined with columnar 
and ciliated cells, evidently tracheal remnants, and even 
crystalline lens, adrenal, and splenic tissue. 

iMeyer, R.: Frankfurt. Ztschr. f. Path., 1913, xiii, 215 (bibl.). 

^Ohkubu: Arch. f. Entwcklng-smechn. d. Organ., 1908, xxvi, 509 
(bibl.); Wilms: Zieg-lers Beitr., 1896, xix, 233; also Die Mischg-eschwtilste, 
Leipzig-, 1899-1902; Ewing: Surg., Gynec, and Obst., 1911, xii, 230 (bibl.). 

^Bulkley: Surg., Gynec, and Obst., 1913, xvii, 703. 

*Chevassu: Tumeurs du Testicule, These de Paris, 1906. 

205 



The clinical development of these teratomata is slow; 
many of them are present at birth, and remain benign for 
years, but occasionally an alteration in the biology of the 
tumor has been observed, with rapid growth and the forma- 
tion of metastases. 

Tumors of the second group resemble the solid terato- 
mata of the ovary in that they consist of a mixture of 
tissues without the formation of adult structures. There 
may be numerous cysts or tubules lined with squamous or 
high cylindrical cells, islands of squamous cells, and rem- 
nants of smooth muscle, connective tissue, osteoid tissue, 
and cartilage. Neuroepithelial areas are not at all infre- 
quent and fragments suggestive of the gastrointestinal 
tract are occasionally present. These tumors, also, are rare 
and apt to be more malignant than the first type, especially 
if chorionepitheliomatous changes occur.^ The exact his- 
togenesis of the syncytial cells is not fully determined. 
They often form small areas lining blood-containing cavi- 
ties. It has been thought that they were derived from the 
neuroepithelial areas, while others believe that they come 
from the epithelium of the testicular growth. Biologically, 
the tumor acts in the same fashion as the chorionepithelio- 
mata of the pregnant uterus, and there is but little doubt 
of the similarity of the two conditions. Other portions of 
the tumor may metastasize into the same organ with the 
choriomatous fraction. 

The third variety of testicular tumor is the most fre- 
quent, and is composed of large round or polyhedral cells 
not resembling very closely any normal cell of the testicle, 
though suggesting to a certain extent those lining the 
seminal tubules. The neoplastic cells lie either in alveoli 

*Pick: Virchows Arch. f. path. Anat., 1905, clxxx, 172; Schlagenhaufer: 
Wien, klin, Wchnschr., 1902, xv, 571; Frank, R. T.: Jour. Am. Med. Assn., 

1906, xlvi, 256 (bibl.); Risel: Lubarsch-Ostertag, Ergebn. der allg-. Path., 

1907, xi2, 928; Cooke: Bull. Johns Hopkins Hosp., 1915, xxvi, 215 (bibl.); 
W^oglom: St. Luke's Hospital Medical and Surgical Reports, New York, 
1917, iv, 188 (bibl.); Meyer: Frankfurt. Ztschr. f. Path., 1913, xiii, 215. 

206 



or diffusely scattered throughout the stroma of the tumor. 
Ewing calls the type an embryonal carcinoma; Chevassu, a 
seminoma. The tumor is rapidly growing, and on cut sec- 
tion is soft, opaque, and often necrotic with large hemor- 
rhagic areas. In fact, it is often difficult to find well pre- 
served tissue for microscopical examination, except small 
areas remaining about the vessels. Only a portion of the 
testis may persist as a thin covering to the tumor, or it 
may simply be pushed to one side. Special stains, such 
as Bielschowsky's silver method or Mallory's aniline blue 
stain for connective tissue, show a certain number of fine 
fibrils lying at the periphery of the alveoli, or, if the tumor 
is diffuse, lying between most of the cells. On the other 
hand, a certain number of alveoli may be found free of 
connective tissue with the cells lying in contact. For the 
latter reason, the general tendency is to designate these 
tumors as carcinomata rather than sarcomata. The tumors 
are highly malignant, although a number of recoveries have 
been reported after operation. The metastases usually re- 
semble those of the primary tumor ; some of them, however, 
are strikingly like lymphoblastoma. 

Cystic Teratoma of the Ovary 

The dermoid cysts of the ovary, or embryomata, are a 
cystic form of teratomata, and thus not wholly tumors in 
the pathological sense, but rather one-sided products of the 
development of cells of great tissue potency existing in the 
ovary.^ The term dermoid is a very old one, given because 

^See, for very complete review of the subject of ovarian dermoids with 
extensive bibliography, the chapter by Kxoemer in Veit's Handbuch d. 
Gynec, Wiesbaden, 1909, iv, part 1, 206. See, also, the chapter on dermoid 
cysts by Williamson in Eden and Lockyer's A System of Gynaecology, 
London, 1917, ii, 787; Leipmann: Handbuch der Frauenheilkunde, Leipzig, 
1914, ii, 216; Askanazy: Dermoid cysts of the ovary, Bibliotheca medica, 
Abth. C, Heft 19, Stuttgart, 1905; and Ewing: Neoplastic Diseases, Phila- 
delphia, 1919, p. 593. 

207 



of the presence of skin and hair in these tumors, and though 
inaccurate is still in general use. 

These tumors constitute about 10 per cent, of all 
ovarian neoplasms. They appear at all ages, not infre- 
quently in childhood, but are found most often between 
the ages of thirty and forty. While early growth may be 
rapid, the cysts soon reach a limit and may remain sta- 
tionary for many years. They may be single, as is 
most frequently the case, bilateral, or multiple. They 
may be combined with other types of cysts, such as 
the cystadenomata or the simple ovarian cysts. The cavi- 
ties may remain distinct, or the walls between the two cysts 
may be broken down by infectious or necrotic processes, 
with the result that they may have a common lumen with 
mixed contents. The cysts may become infected ; they may 
rupture into the peritoneal cavity and give rise to a chronic 
peritonitis due to irritation of the fat and cholesterol which 
they contain; they may perforate into the uterus, into the 
rectum, or the bladder. In size, they vary from growths 
a centimeter or more in diameter to tumors the size of a 
man's head or larger. Macroscopically, they are oval or 
spherical encapsulated masses which entirely involve the 
structures of the ovary or leave remnants of the gland on 
ine side of the tumor. The capsule is usually thin, well 
>rascularized, whitish or greyish, and in one portion of the 
wall there is almost invariably a thickened area which can 
be seen upon opening the cyst. From this **head" spring, 
as a rule, bundles of fine hair, and undei its epithelial cov- 
ering may be found the various tissues of a mature type 
which make up the characteristic constituents of the der- 
moid cyst. If the tumor is opened while it is still at body 
temperature, the contents will be found to be largely fluid 
oil which solidifies as cooling takes place. Usually, how- 
ever, there is in addition to this fatty material a large 

208 



amount of desquamated epithelium, cholesterin crystals, 
and detritus of all sorts. Hemorrhage occasionally occurs 
with the formation of much brownish pigment from modi- 
fied hemoglobin. Various types of structures can be demon- 
strated in the solid portion of the cyst. wall. Some con- 
tain only hair springing from a nodule on one side of the 
cyst. This nodule is usually covered with epidermis and 
may contain only a little fibrous tissue, bone, or bony struc- 
tures. The hair may be white even in the dermoids of 
young persons, but is usually of other colors. It may lie 
free in the cavity of the dermoid, or in granulation tissue 
on the wall, where it has been caught after being shed from 
the part in which it grew. Here it frequently gives rise 
to granulation tissue with large numbers of giant cells 
which coat the surface of the irritating hair. Teeth have 
often been found situated in irregular pieces of bone, and 
it is probable that both milk teeth and adult teeth may be 
formed, for smaller dental structures have been found free 
in the cyst when mature teeth were present in the bone. 
In addition, it is sometimes possible to identify portions of 
fingers, intestine, brain, eye, and thyroid gland. The latter 
may even make up a considerable portion of the tumor. 
Cartilage, also, is frequent and sometimes easily visible in 
the gross. 

Microscopically, the most striking thing about dermoid 
cysts is that most of the tissues are adult in type. The 
list of those found would include almost every known struc- 
ture with the exception of the genital glands. The most 
frequent are sebaceous and squamous glands of the skin, 
portions of salivary glands, thyroid tissue, glia or occasion- 
ally brain tissue with well developed ganghon cells, bone, 
and cartilage. Intestinal fragments are not infrequent; 
ciliated epithelium lining nasal or tracheal remnants is 
often present, as well as striated muscle fibers. The variety 

209 



of the different types of tissue which can be demonstrated 
is largely in proportion to the number of sections of the 
tumor which are thoroughly studied. It is evident that a 
dermoid cyst is an attempt at growth of an abortive fetus, 
only the head end of which develops. 

The explanation of the condition is difficult. It is 
usually assumed that such a tumor must arise from a cell 
which is totipotent, that is, contains within itself the capac- 
ity of almost all types of tissue. This means, therefore, 
that the cell must have been left in the ovary or formed 
in it at an early stage of development. Three possibilities 
are usually considered as explaining these tumors. The 
older and now abandoned view was that polar bodies, after 
they are set free, are capable of further development. An- 
other view is that unused blastomeres of high potency are 
left in the ovaries during the course of its formation; the 
third, and the one to which at the present time most path- 
ologists adhere, is that these complex tumors and the solid 
teratomata of the ovary, which will be discussed in the next 
paragraph, are derived from ova which undergo in some 
fashion a parthenogenetic stimulus to development, and 
as the result of that development form a rudimentary fetus. 
The whole question is still in the stage of pure speculation 
and awaits experimental investigation along the line which 
Jacques Loeb, Leo Loeb, and Bataillon have pursued with 
such success. 

The clinical course of the ovarian dermoids is, as a rule, 
benign, though they may cause considerable disturbance by 
pressure on a neighboring organ, by the presence of bacteria 
and resulting suppurative processes, or by rupturing into 
the neighboring hollow viscera; but, as a rule, after 
removal, no further symptoms are to be expected. In a 
fairly large number, perhaps a maximum of 1 per cent, of 

210 



ovarian dermoids, malignant changes occur with the devel- 
opment, most frequently, of squamous-cell epitheliomata 
from the epidermal fraction or, much more rarely, of tumors 
of a sarcomatous nature from the connective tissue part. 
These tumors are highly malignant, are usually not recog- 
nized until they have involved the neighboring lymph-nodes 
or other organs, and almost always cause the death of the 
patient. 

The diagnosis of the uncomplicated dermoid cysts is 
easy and usually is made wholly upon the gross morphology. 
In cases of doubt, microscopic examination of the head pro- 
tuberance from which the hair grows will give confirmatory 
evidence of the complex nature of the growth. 

Solid Teratoma of the Ovary 

These tumors, in comparison with the dermoids of the 
ovary with which they are closely related in origin, are 
very rare and of infrequent occurrence. They are usually 
spherical, encapsulated, fairly firm tumors of moderate size, 
rarely reaching the dimensions of the largest ovarian cysts, 
but exceeding the average of the latter. They are not so 
frequently bilateral as are the dermoids, and are not mul- 
tiple. In contrast to the dermoid cysts, most of the cases, 
and they are still relatively few, not over fifty such tumors 
having been observed, have occurred in the earlier periods 
of life. Seven have been reported before the age of fifteen 
years. They grow with extreme rapidity from their incep- 
tion, and act in all instances as malignant tumors. About 
one quarter of the patients upon whom operations have 
been performed, however, have lived for a number of years. 
In keeping with these clinical qualities, metastases are 
found early. They may be sarcomatous or carcinomatous. 

211 



Microscopically, these tumors vary greatly in different 
portions, some areas being hard, bony, or cartilaginous, 
though these tissues are less frequent than in the dermoids. 
Hair is rarely present. Most of the tissues found are em- 
bryonic in type and are mixed together and not arranged 
in any way which suggests an attempt to form mature 
structures. It is, therefore, not uncommon to find striated 
muscle, myxomatous tissue, portions of brain, dura, epithe- 
lial elements, and pigmented cells, possibly related to the 
choroid of the eye, and usually, in addition, areas suggest- 
ing carcinoma or sarcoma. The metastatic tumors as stated 
are usually sarcomatous or carcinomatous, but myxomatous, 
cartilaginous, cystic, and glial metastases, and even some 
containing intestinal wall and striated muscle have been 
observed. As a rare change, chorionepithelioma of the 
same nature as that arising in the teratomata of the thorax 
and of the testicle has been found to develop in these tera- 
tomata, and form metastatic nodules throughout the body. 

The diagnosis of tumors of this type is, of course, im- 
possible without microscopic study, and with such assist- 
ance is not always simple. Metastases removed for exami- 
nation do not reveal the nature of the primary growth, be- 
cause they may be, as obsen^ed, carcinomatous, sarcoma- 
tous, gliomatous, or chorionepitheliomatous.^ 

Thyroid Teratoma of the Ovary 

Closely connected with the teratomata of the ovary 
are tumors composed largely of thyroid tissue,^ and others 
in which the suprarenal gland structures apparently are 
part of the neoplasm. These gro\\i:hs are supposed to be 

iFrank, R. T. : Am. Jour. Obst., 1907, Iv. 348 (bibl.); SjovaU: Frankfurt. 

Ztschr. f. Path., 1911, vii, 10 (very good bibl.). 

^Trapl: Ztschr. f. Geburtsh. u. Gynak., 1912, Ixx, 192. 

212 



derived from a teratoma of which only one tissue has sur- 
vived. A similar explanation has been offered for the pecu- 
liar histologic structure of the cystadenoma of the ovary, 
the theory being that the tissues are derived from embryo- 
nal development of rudiments of intestine present in a tera- 
toma. This last statement is not generally accepted by 
pathologists, but the explanation of the thyroid and adrenal 
tumors is quite generally received. 

The thyroid tissue may be small in amount and repre- 
sent part of a dermoid, or it may form the whole of a solid 
tumor, or finally it may be a part of a large single or multi- 
locular cyst. Large areas of colloid are often present, and 
the tissue contains iodine. While thyroid ovarian terato- 
mata are not rare, only a few have developed carcinoma. 

Cystic or Solid Teratomata Containing Adult Tissues 
Sacral Teratoma 

The teratomata which occur in the sacral region are 
the best examples of the type in which the tendency is to 
produce remnants of mature organs and highly adult 
tissues. These tumors are rare and form a heterogeneous 
group, as the several structures are in very different stages 
of development in the examples which have been studied, 
no two being exactly the same.^ The tumors may be solid 
or cystic. They lie, as a rule, at the lower end of the spinal 
column in front of the sacrum and coccyx, displacing the 
anus forward, but may also extend over the dorsal surface 
of the bone. Most of them appear in young children or in 
stillborn fetuses. The tumors are usually encapsulated. 
On cross section, they show extremely varying structures, 

^Borst: Centralbl. f. allg-. Path., 1898, ix, 449; Nakayama: Arch. f. 
Entwcklng-smechn. d. Organ., 1905, xix, 475; Hag-en: Beitr. f. klin. Chir., 
1904, xlii, 646; Englemann: Arch. f. klin. Chir., 1903-04, Ixxii, 942; Schramm: 
W^ien. klin. Wchnschr., 1910, xxiii, 65. 

213 



cysts lined with cubical, ciliated, or squamous epithelium, 
sebaceous material, hair, and sweat glands, cartilage, bone, 
lymphoid tissue, areas of gliar tissue and neuroepithelium, 
pigment structures, and occasionally, well developed teeth 
and bone. 

A type containing more mature tissues or rudimentary 
organs is usually found on the posterior surface of the 
sacrum and coccyx, being connected with the bone by means 
of a pedicle. While the cystic and solid portions are similar 
to those tumors just described, there may be found, in 
addition, fragments of intestine, esophagus, stomach with 
smooth muscle tissue, gland, lung tissue, pancreas, spleen, 
adrenal, kidney, brain and choroid plexus. The develop- 
ment of the bony structures and muscle may result in the 
formation of complete limbs and even eyes have been found. 

Evidently these tumors are transitions between the 
sacral twins and the teratomata. The origin of the tumors 
is still in question, but some of the simple forms are usually 
assumed to be due to the displacements of remnants of the 
neurenteric canal, the post-anal gut, and other structures 
which are present in this complex region during embryonic 
development ; others to dislocated blastomeres, and the more 
mature to rudimentary twins. 

In addition to the teratomata of the sacral region simi- 
lar growths appear in various portions of the body. 
Among these are the epignathi, tumors of considerable size 
which are found about the head and in the mouth and neck. 
They are covered with skin and sometimes show develop- 
ment of extremities of a second individual. Others con- 
train no adult tissue, but are composed of a mixture of rudi- 
mentary glands, epithelium, bone, cartilage, muscle, and 
central nervous system. There are similar teratomata oc- 
curring in the thyroid gland composed of varying propor- 
tions of nerve tissue, bone, teeth, and gastrointestinal tract. 

214 



An analogous teratoma has been seen in the cavity of the 
skuU.i 

In addition to complex tumors of this variety a few 
teratoid tumors have been found in the abdominal cavity, 
which are composed either of partially developed fetuses or 
mixtures of various tissues.^ 

Mediastinal teratomata are fairly frequent and are com- 
posed of a great variety of tissue including those of the 
nervous system, connective tissue, bone, cartilage, and so 
on, and, in some instances they have developed into a 
chorionepithelioma, lymphosarcoma, or spindle-cell sarcoma, 
and caused the death of the patient by the extension of the 
malignant growth.^ 

CYSTS 

Cysts are neoplastic structures which, for the sake of 
convenience, are usually considered with the tumors, al- 
though many of them differ from true neoplasms in char- 
acter and histological composition, and in some instances, 
in their genetic relationships. On the other hand, there 
are tumors which are always cystic, for example, the der- 
moid teratomata of the ovary. A cyst is defined as a spheri- 
cal, or approximately spherical, body which possesses a 
sharply defined wall and more or less homogeneous con- 
tents, usually of fluid or soft consistency. True cysts are 
lined either with epithelium or endothelium. False cysts 
are not so lined, and arise by a collection of fluid in solid 
tissue, due to softening or retention of secretion. It should 

^Lovett and Councilman: Jour. Exper. Med., 1897, ii, 427 (possible 
metastasis in head from testicular tumor). 

^Montgomery and Barker: Jour. Exper. Med., 1898, iii, 259, 284; Lexer: 
Arch. f. Chir., 1900, Ixi, 648; 1900, Ixii, 351. 

sprym: Frankfurt. Ztschr. f. Path., 1914, xv, 182; Christian: Jour. 
Med. Research, 1902, N. S. ii, 54; Hertzler: Am. Jour. Med. Sc, 1916, 
clii, 165; Dangschaat: Beitr. z. Klin, Chir., 1903, xxxviii, 692. 

215 



be remembered, however, that in many true cysts the epi- 
thelial lining may desquamate under inflammatory condi- 
tions. Cysts may be divided into five classes:^ 

I. Cysts which develop in pre-existing cavities : 

1. Retention cysts. These are formed by the accumu- 
lation of the secretions in glands or their secretory ducts 
as the result of obstruction to the normal discharge of 
secretion, inflammatory reaction, or pressure. The con- 
tents may be mucous, sebaceous, serous, or complex. In 
this class of cysts are the comedones, milium, atheroma, 
ranula, ovula Nabothi, milk cysts of the breast, and serous 
cysts of the ovary. Fallopian tubes, and uriniferous tubules. 
Chalazion, occasionally included in this group, is due to a 
productive giant-cell inflammation in a Meibomian gland, 
and is a granuloma rather than a cyst. 

2. Transudation cysts. These forms arise usually, 
though not always, as the result of a chronic inflammatory 
process in the tissue, lymph-spaces, or serous cavities. 
Among such cysts may be included ganglion of the tendon 
sheaths, hydrocele, etc. When blood is extravasated into 
closed cavities a wall may form and the blood be absorbed, 
giving rise to a type of cyst derived originally from a 
hematocele. 

II. Cysts which originate independently as the result 
of pathological change. 

1. Cysts formed by softening and disintegration of 
tissue. Cysts of this type are usually small at first with 
only a moderate amount of contents and no well defined 
walls. The wall finally develops either as an entirely new 
structure or as a more or less modified capsule derived from 
the organ in which it has occurred. One example in which 
the wall is formed by the action of parasites is the ordinary 

^For details concerning cysts which cannot be considered here, see 
Ewing: Neoplastic Diseases, Philadelphia, 1919 (bibl.); and Aschoff: Lu- 
barsch-Ostertag, Ergebn. d. allg. Path., 1895, ii, 456 (bibl.). 

216 



echinococcus cyst of the liver. The contents of such cysts 
are the detritus of the tissue in which the cyst is formed, 
usually accompanied by blood, leucocytes, and cholesterol 
which crystallizes out from the contents of the cyst in the 
course of inspissation of the exudate. Cysts of this type 
may occur in tumors which are rapidly growing and poorly 
vascularized, and, therefore, very subject to degeneration. 
Cysts may appear, also, in the slow-growing tumor-like 
masses involving the bone in osteitis fibrosa, or in clefts of 
the softenings in central chondromata which occur near 
the epiphyses. Abscesses may ultimately be transformed 
into well marked cysts, especially in the brain where the 
purulent exudate is finally completely absorbed and replaced 
by clear fluid, or the material may remain putty-like, or may 
become calcified. 

III. Cysts formed around foreign bodies. The presence 
of foreign bodies of various types in connective tissue of 
an organ induces an inflammatory reaction which may re- 
sult in well defined cysts. Such cysts are formed about 
parasites, notably the echinococcus. They are frequent 
about metallic foreign bodies, such as needles, bullets, etc., 
and belong to the group of false cysts because they are not 
lined by epithelium or endothelium. 

IV. Cysts formed by new growth of tissue in whose 
spaces various kinds of fluids accumulate. These may or 
may not be lined with epithelium, and are usually due to 
the tumor-like process. Such forms are exemplified in the 
cystadenomata of the breast and the ovarian cystomata 
which, also, are related to the adenomata. 

V. Cysts of congenital origin. These cysts are of vari- 
ous forms and their mode of origin is often but imperfectly 
understood. They may be grouped as follows : 

1. Epidermoid cysts of the skin which are due to a 
congenital displacement of the epidermis occurring along 

217 



the junction planes of the face or body during development. 
Hence the cysts lie about the outer comer of the eye, for 
instance, or on the perineum or scrotum. 

2. Dermoid cysts which show skin, papillae, glands, 
and hair in the wall, demonstrating that a considerable pro- 
portion of the derma has been turned in to form the wall 
of the cysts. 

3. Complex dermoid cysts, really teratomata, such as 
those of the ovary, mediastinum, sacrum, and so on, which 
have been described under teratomata. 

4. Cysts formed in the branchial clefts, either epider- 
moid or lined with cylindrical or ciliated epithelium. 

5. Congenital lymph cysts, such as hygroma colli. 

6. The large chylous cysts seen in the mesentery and 
omentum.^ 

7. The congenital cystic kidney and the congenital 
cystic liver, due to incomplete development of essential 
structures in these organs with subsequent accumulation 
of fluid. 



^Niosi: Virchows Arch. f. path. Anat., 1907, cxc, 217 (bibl.) 

218 



INDEX 

Page. 

Adenoma 152 

Adenomyoma 121 

Alveolar sarcoma 101 

Angioma 85 

Angiosarcoma 100 

Animals, tumors in 62 

Bibliography 4 

Biology of tumors, general 6 

Biology of tumors, special 17 

Branchiogenetic cysts 203 

Cachexia 60 

Carcinoid tumors 179 

Carcinoma „ 162 

Carcinoma 172 

Carcinoma, cylindrical-cell 173 

Carcinoma, glandular 175 

Carcinoma, types of.. , 165 

Carcinosarcoma 180 

Chemistry of tumors 31 

Chloroma 109 

Cholesteatoma 151 

Chondroma 78 

Chondrosarcoma « 9 7 

Chordoma 81 

Chorioma 182 

Chorionepithelioma 182 

ChromaflBn tumors 141 

Chromatophoroma 124 

Classification of tumors 7 

Congenital cysts 203 



Connective tissue tumors 9 

Cylindrical-cell carcinoma 173 

Cysts 215 

Cysts, branchiogenetic 203 

Cysts, congenital 203 

Cysts, dermoid 195 

Cysts, epidermoid 194 

Degeneration in tumor tissue 58 

Dermoid cysts 195 

Disappearance, spontaneous, of tumors 36 

Endothelioma 129 

Epidermoid cysts 194 

Epithelial tumors 10 

Epithelioma 167 

Epithelium and connective tissue, tumors of 143 

Etiology of tumors 17 

Fibroma 65 

Fibromyoma 115 

Ganglioneuroma 140 

Giant-cell sarcoma 98 

Glandular carcinoma 175 

Glioma 133 

Hemangioma 86 

Heredity and cancer 24 

Hypernephroma 189 

Immunity in cancer 32 

Increase in cancer 25 

Kidney, complex tumors of 200 

Leiomyoma 115 

Leukemia Ill 

Lipoma 73 

Lymphangioma 88 

Lymphoblastoma 101 

Lymphocytoma 101 

Lymphoma 101 

Lymphosarcoma 101 

Malignancy „ 61 



Melanoma „ 124 

Metastasis 41 

Metastasis by implantation 54 

Metastasis, mechanism of 42 

Metastasis, organs involved by 56 

Mole : 147 

Multiple primary neoplasms 37 

Muscle tissue, tumors of 113 

Myeloma 107 

Myoma 113 

Mjroma, adeno- 121 

Myoma, fibro- 115 

Myoma levicellulare 115 

Myoma, malignant 123 

Myoma, rhabdo- 115 

Myosarcoma 123 

M3rxoma 69 

Myxosarcoma 98 

Naevus 147 

Nerve structures, tumors of 133 

Neuroblastoma 138 

Neurocytoma 138 

Neuroma 142 

Odontoma 148 

Organism, effect of tumors on 58 

Osteoma 82 

Osteosarcoma 95 

Ovary, cystic teratoma of „ 207 

Ovary, solid teratoma of 211 

Ovary, thyroid teratoma of 212 

Papilloma 143 

Paraganglioma 141 

Paraganglioma of the carotid gland 142 

Phaochromoblastoma 141 

Pigment cells, tumors of 124 

Plasmocytoma 107 

Psammomata 131 



Rhabdomyoma 113 

Round-cell sarcoma 101 

Sacral teratoma 213 

Salivary glands, complex tumors of 198 

Sarcoma ...-.*. 90 

Sarcoma, alveolar 101 

Sarcoma, angio- 100 

Sarcoma, carcino- 180 

Sarcoma, chondro- 97 

Sarcoma, giant-cell 98 

Sarcoma, lympho- 101 

Sarcoma, myo- 123 

Sarcoma, mj^o- 9 8 

Sarcoma, osteo- 9 5 

Sarcoma, round-cell 101 

Sarcoma, spindle-cell 9 2 

Spindle-cell sarcoma 92 

Sympathoblastoma 139 

Teratoma 191 

Teratoma, cystic, of ovary 207 

Teratoma, sacral 213 

Teratoma, solid, of ovary 211 

Teratoma, thyroid, of ovary 212 

Teratomata 11 

Testis, complex tumors of 204 

Thyroid teratoma of ovary 212 

Transfer of tumor cells through the lymphatics 48 

Trauma and tumors 26 

Uterus, complex tumors of 202 

Vagina, complex tumors of 202 

Xanthoma „ 75 



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